Role of zinc in atherosclerosis: a narrative review

Introduction

Background

Atherosclerosis is a chronic cardiovascular disease (CVD) with a high mortality rate worldwide. Many risk factors contribute to the onset of atherosclerosis, including age (1), gender (2), unhealthy lifestyle habits such as smoking (3), and metabolic abnormalities such as diabetes mellitus (4). The progression of atherosclerosis is complex and involves many factors such as oxidative stress, inflammation, dyslipidemia, hypercholesterolemia, and environment (5). Among the essential trace elements implicated in the pathophysiology of atherosclerosis, zinc plays a key role in maintaining vascular health and combating atherosclerosis (6).

Rationale and knowledge gap

Zinc is an important micronutrient in the human body. It acts as a cofactor for many enzymes and is crucial for the integrity and function of cell membranes (7). It is closely related to many key physiological functions, such as immune function (8), oxidative stress (9), and lipid metabolism (10). Zinc plays a critical role in maintaining the structural integrity and function of the vascular endothelium (11). Currently, evidence focusing on the relationship between zinc status and atherogenic risk factors has been well established (12), while the direct interaction between zinc and atherosclerosis has not been fully understood.

Objective

In this review, we explore the complex relationship between zinc and atherosclerosis, revealing the mechanisms by which zinc modulates key pathways involved in the development of atherosclerotic plaques. We assess the current evidence on the effects of zinc on oxidative stress, inflammation, endothelial function, and lipid metabolism in the context of atherosclerosis. Simultaneously, we also summarize the additional treatment methods that utilize zinc as a potential therapeutic target for the prevention and management of atherosclerotic CVD (ASCVD). We present this article in accordance with the Narrative Review reporting checklist (available at https://jxym.amegroups.com/article/view/10.21037/jxym-24-57/rc).

Methods

A literature search was conducted on PubMed, Medline, Cochrane, Embase, and Google Scholar for studies published between December 8, 2010 and February 25, 2025, using keywords related to zinc deficiency, zinc overload, zinc levels, zinc supplementation, and oxidative stress in atherosclerosis. Publications in English language or those which had English language translation were included in the analysis. The excluding criteria were as follows: retracted articles, letters to the editor, case reports, or duplicate studies. Two authors (T.D. and G.Z.) independently searched the literature and after elimination of duplicate articles evaluated the eligibility of papers according to the abovementioned criteria. The other two authors (M.D. and S.D.) extracted data from each article included in the review (Table 1).

Discussion

Function, transportation, and homeostasis of zinc

Function of zinc

Zinc has several key functions, including enzyme function, immune function, growth and development, wound healing, and perhaps most importantly, antioxidant defense (13) (Figure 1).

Figure 1 Function of zinc. Zinc aids thymulin production for lymphocyte maturation and immunity. It’s essential in signaling and inhibits inflammatory cytokines, blocking the NF-κB pathway. It also supports antioxidant production to prevent oxidative stress. In cooperation with metals like calcium, zinc assists IGF-1 production for angiogenesis and boosts collagen for wound healing. Created with Biorender. GPx, glutathione peroxidase; IGF-1, insulin-like growth factor 1; NF-κB, nuclear factor-κB; ROS, reactive oxygen species; SOD, superoxide dismutase; TNF, tumor necrosis factor; Zn, zinc.

Zinc is a component of more than 300 enzymes in our bodies and is involved in the activities of many enzymes (14), and it has only one stable oxidation state, Zn (II). Changes in zinc concentration often stimulate both non-specific and specific immunity (15). Zinc decreases nuclear factor-κB (NF-κB) activation and its target genes, such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β, and increases the gene expression of A20 and peroxisome proliferator-activated receptor-α (PPAR-α), the two zinc finger proteins with anti-inflammatory and growth promotion properties (16).

Zinc is associated with many metalloenzymes and is necessary for the synthesis of proteins (17). Zinc is also involved in the synthesis of DNA to ensure proper replication and neurological development (18).

When it comes to wound healing, zinc helps in the synthesis of collagen, a key component of the structural framework of connective tissues such as skin, which is essential for wound healing and tissue repair (19). The current study shows that zinc is a promising alternative to conventional materials for the production of absorbable weight-bearing sutures, internal and subcutaneous nails (20). Zinc also stimulates the formation of new blood vessels at the wound site (angiogenesis) and the proliferation and migration of various cells involved in wound healing, including fibroblasts, epithelial cells, and immune cells (21,22). Alongside zinc, enzymes such as metalloproteinases contribute to the breakdown and remodeling of damaged tissue to form new healthy tissue and to the recovery of atherosclerotic diseases (23). Zinc is an essential micronutrient in antioxidant defense mechanisms and plays a crucial role in maintaining the balance between oxidative stress and antioxidant protection (24). Higher concentrations of zinc enhance the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx), both of which form a barrier against reactive oxygen species (ROS) (25). ROS molecules, including superoxide, hydrogen peroxide, and hypochlorous acid, are all implicated in the pathogenesis of atherosclerosis through their roles in oxidative stress, inflammation, and lipoprotein modification (26). Increased intake of zinc can help maintain the oxidative/antioxidative balance and has a protective effect when this balance is disrupted (27).

As an important factor in combating oxidative stress, zinc acts as a cofactor in many antioxidant enzymes, including SOD, catalase (CAT), and GPx (28). These enzymes help neutralize ROS and protect cells from oxidative damage (29). Additionally, zinc plays a crucial role in reducing the concentration of thyroid-stimulating hormone (TSH) in the body (30). TSH can cause ROS aggregation and accelerate mitochondrial apoptosis, thereby promoting the oxidative process (31). Previous experimental and clinical studies have found that zinc supplementation can enhance antioxidant capacity and mitigate oxidative stress (32-34). Through these kinds of functions, zinc is directly associated with the development of CVDs including atherosclerosis (35).

Transportation of zinc and zinc homeostasis

The human body cannot synthesize zinc on its own. Therefore, zinc must be obtained from the outside and transported to different destinations within the body. Zinc binding metallothioneins (MTs), zinc-iron permease (ZIP), and zinc transporters (ZnTs) are the proteins involved in zinc transport, and plays a pivotal role in the influx, efflux, chelation, sequestration, and release of zinc (36).

ZIP is a crucial membrane protein involved in the transport of zinc ions into the cytoplasm, usually distributed across cellular membranes (37). There are at least 14 types of ZIP involved in zinc transport, each of which is determined by the corresponding solute-carrier family type 39A (SLC39A) gene family (38).

The mechanism of ZIP transporters involves the recognition, binding, and translocation of zinc ions on lipid bilayer membranes to transfer zinc from the extracellular space or intracellular organelles into the cytoplasm (39). ZIP transporters are composed of multiple transmembrane domains (TMDs) that span the cell membrane, and can provide channels or pore-like structures through which zinc ions can pass (40).

There are two main ways for ZIP protein to transport zinc: diffusion facilitation and active transport (41). In facilitated diffusion, the concentration gradient of zinc ions drives the process (42). In active transport, ZIP proteins can transport zinc regardless of zinc concentration gradient, requiring energy consumption in the form of adenosine triphosphate (ATP) (43). This allows the cells to accumulate zinc even when zinc concentrations in the extracellular environment are low (44). Both types help maintain the homeostasis of zinc and meet the biological requirements of diverse tissues or organs (45).

ZnT is another important protein family, determined by the corresponding gene in the solute-carrier family type 30A (SLC30A) family (46). These proteins mainly transport zinc from the cytoplasm to the Golgi apparatus or outside the cell (47). Low and high zinc levels can significantly down-regulate the expression of ZnT1 and ZnT2 messenger RNA (mRNA) in smooth muscle cells and endothelial cells (48). Moreover, ZnT can distinguish between Zn²⁺ and the toxic ion Cd²⁺, induces oxidative stress, and is closely related to the atherogenic process (49). ZnT is also a component of many enzymes. The zinc binding site in ZnT contains four conserved hydrophilic coordination residues of TMD5, whose mutations inhibit zinc transport activity (50).

Many ZIP and ZnT transporters have their own specific functions. ZIP1–6, ZIP8–10, ZIP12, and ZIP14 help transport zinc from outside to the cytoplasm, and ZnT1 and ZnT10 help transport zinc from the cytoplasm to the outside of the cell (51) (Figure 2).

Figure 2 Transportation of zinc. Zinc is transported into the cytosol through ZIP1–6, ZIP8–10, ZIP12, and ZIP14 and out through ZnT1 and ZnT10. Zinc is transported into and out of the Golgi apparatus via ZnT5–7 and ZnT10, and ZIP9 and ZIP13. ZnT5–7 also transmit early secretory pathways consisting of zinc enzymes (TNAP). ZnT3 transports zinc into synaptic vesicles, while ZnT9 and ZIP11 handle transportation into and out of the nucleus. Both lysosome and endosome use ZnT2, ZnT4, and ZIP8 for zinc transport, with ZnT10 also functioning in the endosome. By Figdraw. MTs, metallothioneins; TNAP, tissue non-specific alkaline phosphatase; Zn, zinc; ZIP, zinc-iron permease; ZnT, zinc transporter.

MTs can specifically bind to various metal ions, including zinc (52). Cysteine is the most common amino acid in MTs, accounting for 30% of the amino acid content (53). MTs are rich in cysteine and have conserved structures in the body, and play a crucial role in antioxidant defense, promoting antioxidant activity in the body by transporting and regulating zinc levels (54). When bound to zinc, they help to promote the antioxidant process (55). The MTs-zinc complex is essential because it participates in the transport of zinc through different tissues and cells in the body (56). The increase in MTs can clear free radicals and ROS, preventing them from causing damage to cells and tissues (57). This antioxidant activity helps prevent oxidative damage that can lead to atherosclerosis and other CVDs (58). Meanwhile, zinc-containing MTs can modulate the expression of genes encoding antioxidant enzymes and proteins, effective maintaining redox balance (59). Zinc itself can accelerate the synthesis of MTs by activating the zinc-sensing metal regulatory transcription factor 1 (MTF1) (60).

Zinc plays such a crucial role in body signaling and metabolism, and even a slight deficiency or excess can cause cardiovascular imbalance and disease (61). Therefore, maintaining zinc homeostasis is crucial for the prevention of atherosclerosis (62).

In the gastrointestinal tract, zinc homeostasis is primarily maintained (63), with the highest zinc absorption rate in jejunum (64). The duodenum has a higher exposure to zinc after a meal, so it helps to secrete and excrete excess zinc into stool (65). Unless severe zinc deficiency or overload occurs, fecal zinc excretion can regulate its total amount to maintain zinc balance and keep plasma zinc levels stable (66).

Zinc-associated proteins also play a significant role in the absorption and excretion of zinc, contributing to zinc homeostasis (67). ZIP4 is a major transporter that mediates intestinal zinc absorption and is found in enterocytes (68). Another important transporter is ZIP5, which can absorb zinc from the blood circulation (69).

Certain hormones can also impact zinc homeostasis, including insulin, growth hormone, estrogen, and testosterone (70). Insulin influences the expression and function of ZIP4 and ZnT8, affecting the absorption and storage of zinc in various tissues (71). In the liver, the role of growth hormone is more significant, while in reproductive tissue, estrogen regulation through ZnTs such as ZIP4 is more critical (72). In addition, testosterone is a cofactor, especially in men (73).

Relationship between zinc deficiency and overload and atherosclerosis

Zinc deficiency and atherosclerosis

A study conducted about Iraq fast-food workers facing higher health risk of atherosclerosis has come to a clear conclusion (74). The balance of trace elements is disturbed by exposure to heavy metals, including zinc, cadmium, lead, and nickel. We can see that lower zinc levels, reduced by 17% compared to healthy individuals, are associated with a higher risk of developing atherosclerosis (74). This suggests a direct impact of zinc imbalance on disease. In our bodies, zinc indirectly affects many other metabolic processes that also contribute to the development of atherosclerosis.

Firstly, zinc deficiency increases the production of ROS in the following ways. On the one hand, this deficiency can activate more N-methyl-D-aspartate (NMDA) receptors that transport calcium from the extracellular space into the cytoplasm (75). Increased calcium produces more substance P, which activates macrophages and leukocytes, increases free radicals, and results in increased oxidative stress (76). On the other hand, zinc deficiency can activate the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase enzymes and nitric oxide synthase, resulting in the production of more reactive species of oxygen and nitrogen, both of which are involved in the oxidative stress process (77). Furthermore, zinc deficiency can lead to reduced activity of various antioxidant enzymes, including superoxide SOD and CAT, as well as increased ability of many oxidant factors, resulting in increased oxidative stress (78). Zinc deficiency promotes oxidative stress, lipid peroxidation, inflammation, and endothelial dysfunction (79-82).

Oxidative stress promotes recruitment and activation of immune cells, such as monocytes and macrophages (83). These overproduced cells contribute to the formation of fatty streaks and the development of plaques (84). Additionally, ROS can directly modify lipids, proteins, and DNA, further exacerbating the inflammatory response and accelerating the progression of atherosclerosis (85). Conversely, atherosclerosis itself can perpetuate oxidative stress (86). The accumulation of lipids and immune cells in the arterial wall creates a microenvironment conducive to ROS production (87). Furthermore, impaired function of antioxidant systems in atherosclerotic plaques contributes to increased oxidative stress (88).

In conclusion, the interplay between oxidative stress and atherosclerosis involves a complex series of events, including lipid peroxidation or low-density lipoprotein (LDL) oxidation, inflammation, immune cell activation, and modification of cellular components. Consequently, zinc deficiency increases oxidative stress (Figure 3).

Figure 3 The relationship between oxidative stress caused by zinc deficiency and overload and atherosclerosis. Zinc deficiency can result in the activation of more NMDA receptors, NADPH oxidase enzymes, and nitric oxide synthases. This can increase calcium concentration, boosting substance P levels and raising macrophage, leukocyte, and free radical amounts, leading to oxidative stress. The rise in ROS from increased NADPH oxidase enzymes and RNS from increased nitric oxide synthases further contribute to oxidative stress. Zinc deficiency can also reduce antioxidant factor production, like SOD and CAT, augmenting oxidative stress. This stress can induce atherosclerosis through endothelial dysfunction, inflammation, and lipid peroxidation. Created with Biorender. CAT, catalase; NADPH, nicotinamide adenine dinucleotide phosphate; NMDA, N-methyl-D-aspartate; RNS, reactive nitrogen species; ROS, reactive oxygen species; SOD, superoxide dismutase.

Secondly, zinc is essential for vascular function and is involved in the activity of endothelial nitric oxide synthase (eNOS) (89). Moreover, through nuclear factor erythroid 2 (NFE2)-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling pathways, zinc deficiency disrupts the balance of vasoactive factors in the endothelium, increases the production of the vasoconstrictor endothelin-1, and correspondingly decreases the production of vasodilator prostacyclin (86). Both excess and deficient zinc can lead to varying degrees of endothelial dysfunction, and these changes ultimately contribute to inflammation, vasoconstriction, and recruitment of inflammatory cells, thereby promoting the formation of atherosclerotic plaques (90).

Thirdly, zinc deficiency alters lipid metabolism, causing the following related abnormalities (91). Zinc is a crucial cofactor of several enzymes involved in lipid metabolism. For example, zinc deficiency can impair the activity of fatty acid synthase leading to reduced fatty acid synthesis and altered lipid profiles (92). Zinc deficiency reduces the activity of acyl-coenzyme A (acyl-CoA) synthetase and affects the conversion of fatty acids into acyl-CoA, which is essential for energy production and other metabolic pathways (93).

Moreover, zinc is involved in the synthesis and function of apolipoproteins, which are essential for the assembly, secretion, and clearance of lipoproteins in the liver (94). Zinc deficiency can lead to changes in high-density lipoprotein (HDL) and LDL (95). Elevated triglyceride levels can also be seen in this condition, which may occur due to impaired activity of lipoprotein lipase (LPL), an enzyme necessary for the hydrolysis of triglycerides in lipoproteins (96). Due to zinc deficiency, lipid peroxidation increases free radicals and malondialdehyde (MDA), which is a product of lipid peroxidation (97). In addition, while lipid metabolic is abnormal, reduced CAT, glutathione (GSH), glutathione-S-transferase (GST), and SOD activity associated with increased ROS production, thus promoting oxidative stress and atherosclerosis (98).

Fourthly, zinc deficiency impairs immune function and results in chronic low-grade inflammation, which plays a pivotal role in atherosclerosis (99). On one hand, zinc deficiency reduces thymulin activities, influencing the maturation of T-helper cells (100). The products of Th1 cells, namely interferon (IFN)-γ and IL-2 are more produced, and IL-10, IL-6, and IL-4 which are the products of T-helper type 2 (Th2) cells do not change (101). In this way, an imbalance between Th cells is created, harming the recruitment of T-cells (102). On the other hand, together with the reduction of T-cells, there are fewer immature or premature B-cells, and correspondingly fewer mature B-cells to work afterwards (103).

Lastly, zinc deficiency affects platelet function, leading to increased platelet aggregation and activation (104). A lack of zinc can lead to reduced levels of thromboxane A2, affecting the ability of platelets to form blood clots efficiently as well (105). Labile or unbound Zn²⁺ is present in the plasma at micromolar levels but is also detected in atherosclerotic plaques, and released from platelet α granules (106).

Zinc overload and atherosclerosis

Excessive zinc intake, exposure to high levels of zinc through external sources, or impaired zinc metabolism can lead to zinc overload (107). Zinc overload can induce oxidative stress and inflammation, both of which are related to atherogenesis (108).

Zinc overload can occur through the overactivation of zinc potassium channels (109). Normally, most zinc can be sequestered in MTs, but oxidative stress caused by atherosclerosis can separate it from the MTs, and as a result, the concentration of free zinc is elevated (110).

Moreover, zinc overload is associated with endothelial dysfunction, which impairs the ability of blood vessels to relax and constrict properly, and promotes the formation of blood clots (111). Zinc overload can lead to increased production of ROS, causing oxidative stress that damages endothelial cells (112). Zinc overload can also induce endothelial cell apoptosis (113). Zinc overload can disrupt the activity and regulation of matrix metalloproteinases (MMPs), a family of zinc-dependent enzymes that plays a pivotal role in vascular homeostasis, thereby posing a threat to vascular health (114).

Zinc overload not only affects its own metabolism, but also affects the function of other metals, such as copper (115). Zinc overload causes copper deficiency and reduces the expression of copper-dependent enzymes (116).

Zinc-targeted therapy

In recent years, there have been new studies on zinc in the treatment of atherosclerosis (117). Increasing zinc intake as a potential treatment for atherosclerosis has a solid foundation (118). According to the National Health and Nutrition Examination Survey, zinc intake at recommended levels [odds ratio (OR) =0.82; 95% confidence interval (CI): 0.69–0.98] was associated with a 0.82-fold greater than 20% risk of ASCVD over 10 years, regardless of the patient’s gender, age, or lipid-lowering therapy (119).

The first zinc-related target is PSMB8-AS1 (120). The results Apoe(−/−)PSMB8-AS1 (KI) mice exhibited increased atherosclerotic development, plaque vulnerability, and vascular inflammation compared to Apoe(−/−) mice (120). At the same time, PSMB9 deficiency reduced atherosclerotic lesion size, plaque susceptibility, and vascular inflammation in Apoe(−/−) mice (120).

The second target is early growth response-1 (Egr-1), which regulates multiple pro-inflammatory processes, supports the presentation of CVD, and controls zinc finger transcription (121). Through the MEK-ERK-Egr-1 cascade, substances such as Tet methylcytosine dioxygenase 2 (TET2), tribbles homolog 2 (TRIB2), myocardial infarction associated transcript (MIAT), sphingosine kinases type 1 (SphK1), cyclic adenosine monophosphate (cAMP), teneligliptin, cholinergic drugs, red wine and flavonoids, wogonin, febuxostat, docosahexaenoic acid, and angiotensin II type 1 receptor (AT1R) blockade have already been utilized (121).

The third target is related to miR-147a (122). miR-147a attenuates oxidized LDL (ox-LDL)-induced adherence of monocytes to human umbilical vein endothelial cells (HUVECs) and modulates atherosclerotic plaque formation and stability through targeting zinc finger E-box binding homeobox 2 (ZEB2) during atherosclerosis (122).

The fourth target is MMP-2 (123). MMP-2 expression is higher in patients with unstable coronary artery disease (CAD) than those with healthy subjects (123). MMP-2, one kind of ZnTs, plays a crucial role in the development of atherosclerosis among patients with CAD and hence could be a potential target for CAD therapy (124).

The fifth target is about the ZIP family. Although the ZIP family is currently only used to treat various types of cancer, it has the potential to be studied for the treatment of atherosclerotic diseases (38).

As for more gene-related therapies, proprotein convertase subtilisin/kexin type 9 (PCSK9) (125), apolipoprotein C-III (ApoC3) (126), long non-coding RNAs (lncRNAs) especially LeXis with AAV8 (127) and genes regulating liver X receptors (128), are all potential targets of atherosclerosis (more detailed in Table 2).

Moreover, zinc supplements have been included in the treatment of various other diseases (139). Zinc gluconate oral liquid is used to treat malnutrition, anorexia, and developmental delay caused by zinc deficiency in children (140). In addition, people can choose a variety of foods to take zinc supplements (141). Zinc is found in breast milk, seafood such as crustaceans, meat, and nuts (142). Because zinc is always on the move through multiple transporters in the body, mild zinc deficiency is common (143).

Strengths and limitations

The main strength of our study was that our study not only summarized the function of zinc in atherosclerosis, but also explored the relationship between zinc and oxidative stress in atherosclerosis, which may provide a promising treatment method for atherosclerosis. The main limitation of this study was that the references were limited by English language, may have excluded data published in other languages, or had limited identification of relevant long-term follow-up data.

Conclusions

Both zinc deficiency and zinc overload can accelerate atherosclerosis, especially zinc deficiency. Zinc deficiency can lead to increased oxidative stress, impair blood vessel and immune function, alter lipid metabolism, and affect platelet function, thus accelerating the development of atherosclerosis. Besides, zinc supplementation and zinc-related targets as potential treatments for atherosclerosis. It is recommended that people keep their zinc intake stable at 11 mg/day for men and 8 mg/day for women, and no more than 40 mg/day.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://jxym.amegroups.com/article/view/10.21037/jxym-24-57/rc

Peer Review File: Available at https://jxym.amegroups.com/article/view/10.21037/jxym-24-57/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jxym.amegroups.com/article/view/10.21037/jxym-24-57/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Raitakari O, Pahkala K, Magnussen CG. Prevention of atherosclerosis from childhood. Nat Rev Cardiol 2022;19:543-54. [Crossref] [PubMed]
2. Man JJ, Beckman JA, Jaffe IZ. Sex as a Biological Variable in Atherosclerosis. Circ Res 2020;126:1297-319. [Crossref] [PubMed]
3. Ishida M, Sakai C, Kobayashi Y, et al. Cigarette Smoking and Atherosclerotic Cardiovascular Disease. J Atheroscler Thromb 2024;31:189-200. [Crossref] [PubMed]
4. Poznyak A, Grechko AV, Poggio P, et al. The Diabetes Mellitus-Atherosclerosis Connection: The Role of Lipid and Glucose Metabolism and Chronic Inflammation. Int J Mol Sci 2020;21:1835. [Crossref] [PubMed]
5. Libby P. The changing landscape of atherosclerosis. Nature 2021;592:524-33. [Crossref] [PubMed]
6. Li H, Zou J, Yu XH, et al. Zinc finger E-box binding homeobox 1 and atherosclerosis: New insights and therapeutic potential. J Cell Physiol 2021;236:4216-30. [Crossref] [PubMed]
7. Rahimzadeh MR, Rahimzadeh MR, Kazemi S, et al. Zinc Poisoning - Symptoms, Causes, Treatments. Mini Rev Med Chem 2020;20:1489-98. [Crossref] [PubMed]
8. Wessels I, Fischer HJ, Rink L. Dietary and Physiological Effects of Zinc on the Immune System. Annu Rev Nutr 2021;41:133-75. [Crossref] [PubMed]
9. Rabbani E, Golgiri F, Janani L, et al. Randomized Study of the Effects of Zinc, Vitamin A, and Magnesium Co-supplementation on Thyroid Function, Oxidative Stress, and hs-CRP in Patients with Hypothyroidism. Biol Trace Elem Res 2021;199:4074-83. [Crossref] [PubMed]
10. Qi Y, Zhang Z, Liu S, et al. Zinc Supplementation Alleviates Lipid and Glucose Metabolic Disorders Induced by a High-Fat Diet. J Agric Food Chem 2020;68:5189-200. [Crossref] [PubMed]
11. Betrie AH, Brock JA, Harraz OF, et al. Zinc drives vasorelaxation by acting in sensory nerves, endothelium and smooth muscle. Nat Commun 2021;12:3296. [Crossref] [PubMed]
12. Wang Y, Huang N, Yang Z. Revealing the Role of Zinc Ions in Atherosclerosis Therapy via an Engineered Three-Dimensional Pathological Model. Adv Sci (Weinh) 2023;10:e2300475. [Crossref] [PubMed]
13. Zhang C, Dischler A, Glover K, et al. Neuronal signalling of zinc: from detection and modulation to function. Open Biol 2022;12:220188. [Crossref] [PubMed]
14. Cheng Y, Chen H. Aberrance of Zinc Metalloenzymes-Induced Human Diseases and Its Potential Mechanisms. Nutrients 2021;13:4456. [Crossref] [PubMed]
15. Kumari D, Garg S, Bhawrani P. Zinc homeostasis in immunity and its association with preterm births. Scand J Immunol 2022;95:e13142. [Crossref] [PubMed]
16. Jarosz M, Olbert M, Wyszogrodzka G, et al. Antioxidant and anti-inflammatory effects of zinc. Zinc-dependent NF-κB signaling. Inflammopharmacology 2017;25:11-24. [Crossref] [PubMed]
17. Doboszewska U, Wlaź P, Nowak G, et al. Targeting zinc metalloenzymes in coronavirus disease 2019. Br J Pharmacol 2020;177:4887-98. [Crossref] [PubMed]
18. Ho E, Wong CP, King JC. Impact of zinc on DNA integrity and age-related inflammation. Free Radic Biol Med 2022;178:391-7. [Crossref] [PubMed]
19. Adjepong D, Jahangir S, Malik BH. The Effect of Zinc on Post-neurosurgical Wound Healing: A Review. Cureus 2020;12:e6770. [Crossref] [PubMed]
20. Yang N, Venezuela J, Almathami S, et al. Zinc-nutrient element based alloys for absorbable wound closure devices fabrication: Current status, challenges, and future prospects. Biomaterials 2022;280:121301. [Crossref] [PubMed]
21. Nagashima D, Furukawa M, Yamano Y, et al. Zinc-containing Mohs' paste affects blood flow and angiogenesis suppression. Daru 2021;29:321-8. [Crossref] [PubMed]
22. Yang Y, Tai W, Lu N, et al. lncRNA ZFAS1 promotes lung fibroblast-to-myofibroblast transition and ferroptosis via functioning as a ceRNA through miR-150-5p/SLC38A1 axis. Aging (Albany NY) 2020;12:9085-102. [Crossref] [PubMed]
23. Li Y, Hoffman MD, Benoit DSW. Matrix metalloproteinase (MMP)-degradable tissue engineered periosteum coordinates allograft healing via early stage recruitment and support of host neurovasculature. Biomaterials 2021;268:120535. [Crossref] [PubMed]
24. Camp OG, Bembenek JN, Goud PT, et al. The Implications of Insufficient Zinc on the Generation of Oxidative Stress Leading to Decreased Oocyte Quality. Reprod Sci 2023;30:2069-78. [Crossref] [PubMed]
25. Brzóska MM, Kozłowska M, Rogalska J, et al. Enhanced Zinc Intake Protects against Oxidative Stress and Its Consequences in the Brain: A Study in an In Vivo Rat Model of Cadmium Exposure. Nutrients 2021;13:478. [Crossref] [PubMed]
26. Liu J, Han X, Zhang T, et al. Reactive oxygen species (ROS) scavenging biomaterials for anti-inflammatory diseases: from mechanism to therapy. J Hematol Oncol 2023;16:116. [Crossref] [PubMed]
27. Hübner C, Haase H. Interactions of zinc- and redox-signaling pathways. Redox Biol 2021;41:101916. [Crossref] [PubMed]
28. Martins MDPSC, Oliveira ASDSS, Martins MDCCE, et al. Effects of zinc supplementation on glycemic control and oxidative stress in experimental diabetes: A systematic review. Clin Nutr ESPEN 2022;51:28-36. [Crossref] [PubMed]
29. Ali SS, Ahsan H, Zia MK, et al. Understanding oxidants and antioxidants: Classical team with new players. J Food Biochem 2020;44:e13145. [Crossref] [PubMed]
30. Knezevic J, Starchl C, Tmava Berisha A, et al. Thyroid-Gut-Axis: How Does the Microbiota Influence Thyroid Function? Nutrients 2020;12:1769. [Crossref] [PubMed]
31. Peixoto MS, de Vasconcelos E, Souza A, Andrade IS, et al. Hypothyroidism induces oxidative stress and DNA damage in breast. Endocr Relat Cancer 2021;28:505-19. [Crossref] [PubMed]
32. Gulbahce-Mutlu E, Baltaci SB, Menevse E, et al. The Effect of Zinc and Melatonin Administration on Lipid Peroxidation, IL-6 Levels, and Element Metabolism in DMBA-Induced Breast Cancer in Rats. Biol Trace Elem Res 2021;199:1044-51. [Crossref] [PubMed]
33. Sun X, Xu S, Liu T, et al. Zinc supplementation alleviates oxidative stress to inhibit chronic gastritis via the ROS/NF-κB pathway in a mouse model. Food Funct 2024;15:7136-47. [Crossref] [PubMed]
34. Hamedifard Z, Farrokhian A, Reiner Ž, et al. The effects of combined magnesium and zinc supplementation on metabolic status in patients with type 2 diabetes mellitus and coronary heart disease. Lipids Health Dis 2020;19:112. [Crossref] [PubMed]
35. Martinez-Morata I, Schilling K, Glabonjat RA, et al. Association of Urinary Metals With Cardiovascular Disease Incidence and All-Cause Mortality in the Multi-Ethnic Study of Atherosclerosis (MESA). Circulation 2024;150:758-69. [Crossref] [PubMed]
36. Yin S, Duan M, Fang B, et al. Zinc homeostasis and regulation: Zinc transmembrane transport through transporters. Crit Rev Food Sci Nutr 2023;63:7627-37. [Crossref] [PubMed]
37. An Q, Cui C, Muhammad Khan N, et al. Genome-wide investigation of ZINC-IRON PERMEASE (ZIP) genes in Areca catechu and potential roles of ZIPs in Fe and Zn uptake and transport. Plant Signal Behav 2021;16:1995647. [Crossref] [PubMed]
38. Liu H, Li L, Lu R. ZIP transporters-regulated Zn(2+) homeostasis: A novel determinant of human diseases. J Cell Physiol 2024;239:e31223. [Crossref] [PubMed]
39. Thingholm TE, Rönnstrand L, Rosenberg PA. Why and how to investigate the role of protein phosphorylation in ZIP and ZnT zinc transporter activity and regulation. Cell Mol Life Sci 2020;77:3085-102. [Crossref] [PubMed]
40. Hu J. Toward unzipping the ZIP metal transporters: structure, evolution, and implications on drug discovery against cancer. FEBS J 2021;288:5805-25. [Crossref] [PubMed]
41. Mu S, Yamaji N, Sasaki A, et al. A transporter for delivering zinc to the developing tiller bud and panicle in rice. Plant J 2021;105:786-99. [Crossref] [PubMed]
42. Gao L, Li R, Liang Z, et al. Remobilization characteristics and diffusion kinetic processes of sediment zinc (Zn) in a tidal reach of the Pearl River Estuary, South China. J Hazard Mater 2023;457:131692. [Crossref] [PubMed]
43. Barzegar S, Pirouzpanah S. Zinc finger proteins and ATP-binding cassette transporter-dependent multidrug resistance. Eur J Clin Invest 2024;54:e14120. [Crossref] [PubMed]
44. Zhang X, Liu J, Wang J, et al. Adenosine triphosphate (ATP) and zinc(II) ions responsive pyrene based turn-on fluorescent probe and its application in live cell imaging. J Photochem Photobiol B 2021;223:112279. [Crossref] [PubMed]
45. Huang T, Yan G, Guan M. Zinc Homeostasis in Bone: Zinc Transporters and Bone Diseases. Int J Mol Sci 2020;21:1236. [Crossref] [PubMed]
46. Song CC, Chen GH, Zhong CC, et al. Transcriptional responses of four slc30a/znt family members and their roles in Zn homeostatic modulation in yellow catfish Pelteobagrus fulvidraco. Biochim Biophys Acta Gene Regul Mech 2021;1864:194723. [Crossref] [PubMed]
47. Meng J, Wang WX, Li L, et al. Accumulation of different metals in oyster Crassostrea gigas: Significance and specificity of SLC39A (ZIP) and SLC30A (ZnT) gene families and polymorphism variation. Environ Pollut 2021;276:116706. [Crossref] [PubMed]
48. Abdo AI, Tran HB, Hodge S, et al. Zinc Homeostasis Alters Zinc Transporter Protein Expression in Vascular Endothelial and Smooth Muscle Cells. Biol Trace Elem Res 2021;199:2158-71. [Crossref] [PubMed]
49. Tamura Y. The Role of Zinc Homeostasis in the Prevention of Diabetes Mellitus and Cardiovascular Diseases. J Atheroscler Thromb 2021;28:1109-22. [Crossref] [PubMed]
50. Fujishiro H, Miyamoto S, Sumi D, et al. Effects of individual amino acid mutations of zinc transporter ZIP8 on manganese- and cadmium-transporting activity. Biochem Biophys Res Commun 2022;616:26-32. [Crossref] [PubMed]
51. Fujishiro H, Kambe T. Manganese transport in mammals by zinc transporter family proteins, ZNT and ZIP. J Pharmacol Sci 2022;148:125-33. [Crossref] [PubMed]
52. Chen B, Yu P, Chan WN, et al. Cellular zinc metabolism and zinc signaling: from biological functions to diseases and therapeutic targets. Signal Transduct Target Ther 2024;9:6. [Crossref] [PubMed]
53. Miyazaki I, Asanuma M. Multifunctional Metallothioneins as a Target for Neuroprotection in Parkinson's Disease. Antioxidants (Basel) 2023;12:894. [Crossref] [PubMed]
54. Tran HB, Jakobczak R, Abdo A, et al. Immunolocalization of zinc transporters and metallothioneins reveals links to microvascular morphology and functions. Histochem Cell Biol 2022;158:485-96. [Crossref] [PubMed]
55. Álvarez-Barrios A, Álvarez L, García M, et al. Antioxidant Defenses in the Human Eye: A Focus on Metallothioneins. Antioxidants (Basel) 2021;10:89. [Crossref] [PubMed]
56. Aziz J, Rahman MT, Vaithilingam RD. Dysregulation of metallothionein and zinc aggravates periodontal diseases. J Trace Elem Med Biol 2021;66:126754. [Crossref] [PubMed]
57. Arisumi S, Fujiwara T, Yasumoto K, et al. Metallothionein 3 promotes osteoclast differentiation and survival by regulating the intracellular Zn(2+) concentration and NRF2 pathway. Cell Death Discov 2023;9:436. [Crossref] [PubMed]
58. Sarutipaiboon I, Settasatian N, Komanasin N, et al. Association of Genetic Variations in NRF2, NQO1, HMOX1, and MT with Severity of Coronary Artery Disease and Related Risk Factors. Cardiovasc Toxicol 2020;20:176-89. [Crossref] [PubMed]
59. Li Y, Lee SH, Piao M, et al. Metallothionein 3 Inhibits 3T3-L1 Adipocyte Differentiation via Reduction of Reactive Oxygen Species. Antioxidants (Basel) 2023;12:640. [Crossref] [PubMed]
60. Yang Y, Qian Cai Q, Sheng Fu L, et al. Reduced N6-Methyladenosine Mediated by METTL3 Acetylation Promotes MTF1 Expression and Hepatocellular Carcinoma Cell Growth. Chem Biodivers 2022;19:e202200333. [Crossref] [PubMed]
61. Severo JS, Morais JBS, Beserra JB, et al. Role of Zinc in Zinc-α2-Glycoprotein Metabolism in Obesity: a Review of Literature. Biol Trace Elem Res 2020;193:81-8. [Crossref] [PubMed]
62. Dabravolski SA, Sadykhov NK, Kartuesov AG, et al. Interplay between Zn(2+) Homeostasis and Mitochondrial Functions in Cardiovascular Diseases and Heart Ageing. Int J Mol Sci 2022;23:6890. [Crossref] [PubMed]
63. Anderson KJ, Cormier RT, Scott PM. Role of ion channels in gastrointestinal cancer. World J Gastroenterol 2019;25:5732-72. [Crossref] [PubMed]
64. Xiao C, Kong L, Pan X, et al. High Temperature-Induced Oxidative Stress Affects Systemic Zinc Homeostasis in Broilers by Regulating Zinc Transporters and Metallothionein in the Liver and Jejunum. Oxid Med Cell Longev 2022;2022:1427335. [Crossref] [PubMed]
65. Stiles LI, Ferrao K, Mehta KJ. Role of zinc in health and disease. Clin Exp Med 2024;24:38. [Crossref] [PubMed]
66. Wenner BA, Park T, Mitchell K, et al. Effect of zinc source (zinc sulfate or zinc hydroxychloride) on relative abundance of fecal Treponema spp. in lactating dairy cows. JDS Commun 2022;3:334-8. [Crossref] [PubMed]
67. Kim JY, Silvaroli JA, Martinez GV, et al. Zinc finger protein 24-dependent transcription factor SOX9 up-regulation protects tubular epithelial cells during acute kidney injury. Kidney Int 2023;103:1093-104. [Crossref] [PubMed]
68. Ikeda Y, Munekane M, Yamada Y, et al. Enhancing effect of Panax ginseng on Zip4-mediated zinc influx into the cytosol. J Ginseng Res 2022;46:248-54. [Crossref] [PubMed]
69. Hu Y, Wang C, Wu W, et al. Organic zinc with moderate chelation strength enhances zinc absorption in the small intestine and expression of related transporters in the duodenum of broilers. Front Physiol 2022;13:952941. [Crossref] [PubMed]
70. Pascua AM, Nikoloff N, Carranza AC, et al. Reproductive hormones influence zinc homeostasis in the bovine cumulus-oocyte complex: Impact on intracellular zinc concentration and transporters gene expression. Theriogenology 2020;146:48-57. [Crossref] [PubMed]
71. Fukunaka A, Fujitani Y. Role of Zinc Homeostasis in the Pathogenesis of Diabetes and Obesity. Int J Mol Sci 2018;19:476. [Crossref] [PubMed]
72. Sansuwan K, Jintasataporn O, Rink L, et al. Effects of Zinc Status on Expression of Zinc Transporters, Redox-Related Enzymes and Insulin-like Growth Factor in Asian Sea Bass Cells. Biology (Basel) 2023;12:338. [Crossref] [PubMed]
73. Te L, Liu J, Ma J, et al. Correlation between serum zinc and testosterone: A systematic review. J Trace Elem Med Biol 2023;76:127124. [Crossref] [PubMed]
74. Al-Fartusie FS, Mohammed MA, Thani MZ, et al. Evaluation of Heavy Metal and Specific Trace Elements Levels Among Fast-Food Workers and Their Susceptibility to Atherosclerosis. Biol Trace Elem Res 2025;203:1317-26. [Crossref] [PubMed]
75. Starowicz G, Siodłak D, Nowak G, et al. The role of GPR39 zinc receptor in the modulation of glutamatergic and GABAergic transmission. Pharmacol Rep 2023;75:609-22. [Crossref] [PubMed]
76. Zhou Z, Sui X, Cao Z, et al. Substance P promote macrophage M2 polarization to attenuate secondary lymphedema by regulating NF-kB/NLRP3 signaling pathway. Peptides 2023;168:171045. [Crossref] [PubMed]
77. Kaufman Z, Salvador GA, Liu X, et al. Zinc and the modulation of Nrf2 in human neuroblastoma cells. Free Radic Biol Med 2020;155:1-9. [Crossref] [PubMed]
78. Beigi Harchegani A, Dahan H, Tahmasbpour E, et al. Effects of zinc deficiency on impaired spermatogenesis and male infertility: the role of oxidative stress, inflammation and apoptosis. Hum Fertil (Camb) 2020;23:5-16. [Crossref] [PubMed]
79. Zhang Q, Xue Y, Fu Y, et al. Zinc Deficiency Aggravates Oxidative Stress Leading to Inflammation and Fibrosis in Lung of Mice. Biol Trace Elem Res 2022;200:4045-57. [Crossref] [PubMed]
80. Qin X, Zhang J, Wang B, et al. Ferritinophagy is involved in the zinc oxide nanoparticles-induced ferroptosis of vascular endothelial cells. Autophagy 2021;17:4266-85. [Crossref] [PubMed]
81. Rivers-Auty J, Tapia VS, White CS, et al. Zinc Status Alters Alzheimer's Disease Progression through NLRP3-Dependent Inflammation. J Neurosci 2021;41:3025-38. [Crossref] [PubMed]
82. Liu P, Liu J, Wu Y, et al. Zinc supplementation protects against diabetic endothelial dysfunction via GTP cyclohydrolase 1 restoration. Biochem Biophys Res Commun 2020;521:1049-54. [Crossref] [PubMed]
83. Chen Q, Wang J, Xiang M, et al. The Potential Role of Ferroptosis in Systemic Lupus Erythematosus. Front Immunol 2022;13:855622. [Crossref] [PubMed]
84. Remigante A, Spinelli S, Marino A, et al. Oxidative Stress and Immune Response in Melanoma: Ion Channels as Targets of Therapy. Int J Mol Sci 2023;24:887. [Crossref] [PubMed]
85. Hu R, Dai C, Dong C, et al. Living Macrophage-Delivered Tetrapod PdH Nanoenzyme for Targeted Atherosclerosis Management by ROS Scavenging, Hydrogen Anti-inflammation, and Autophagy Activation. ACS Nano 2022;16:15959-76. [Crossref] [PubMed]
86. Zhang Q, Liu J, Duan H, et al. Activation of Nrf2/HO-1 signaling: An important molecular mechanism of herbal medicine in the treatment of atherosclerosis via the protection of vascular endothelial cells from oxidative stress. J Adv Res 2021;34:43-63. [Crossref] [PubMed]
87. Yan R, Zhang X, Xu W, et al. ROS-Induced Endothelial Dysfunction in the Pathogenesis of Atherosclerosis. Aging Dis 2024;16:250-68. [Crossref] [PubMed]
88. Garcia C, Blesso CN. Antioxidant properties of anthocyanins and their mechanism of action in atherosclerosis. Free Radic Biol Med 2021;172:152-66. [Crossref] [PubMed]
89. Barui AK, Bollu VS, Londhe S, et al. Toxicological evaluation of therapeutically active zinc oxide nanoflowers in pre-clinical mouse model. NanoImpact 2023;31:100479. [Crossref] [PubMed]
90. Los J, Mensink FB, Mohammadnia N, et al. Invasive coronary imaging of inflammation to further characterize high-risk lesions: what options do we have? Front Cardiovasc Med 2024;11:1352025. [Crossref] [PubMed]
91. Banaszak M, Górna I, Przysławski J. Zinc and the Innovative Zinc-α2-Glycoprotein Adipokine Play an Important Role in Lipid Metabolism: A Critical Review. Nutrients 2021;13:2023. [Crossref] [PubMed]
92. Xu YC, Zheng H, Hogstrand C, et al. Novel mechanism for zinc inducing hepatic lipolysis via the HDAC3-mediated deacetylation of β-catenin at lysine 311. J Nutr Biochem 2023;121:109429. [Crossref] [PubMed]
93. Yu X, Yang Y, Zhang B, et al. Ketone Body β-Hydroxybutyric Acid Ameliorates Dopaminergic Neuron Injury Through Modulating Zinc Finger Protein 36/Acyl-CoA Synthetase Long-Chain Family Member Four Signaling Axis-Mediated Ferroptosis. Neuroscience 2023;509:157-72. [Crossref] [PubMed]
94. Kim JW, Byun MS, Yi D, et al. Serum zinc levels and in vivo beta-amyloid deposition in the human brain. Alzheimers Res Ther 2021;13:190. [Crossref] [PubMed]
95. Heidari Seyedmahalleh M, Montazer M, Ebrahimpour-Koujan S, et al. The Effect of Zinc Supplementation on Lipid Profiles in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Dose-Response Meta-Analysis of Randomized Clinical Trials. Adv Nutr 2023;14:1374-88. [Crossref] [PubMed]
96. Beloucif A, Kechrid Z, Bekada AMA. Effect of Zinc Deficiency on Blood Glucose, Lipid Profile, and Antioxidant Status in Streptozotocin Diabetic Rats and the Potential Role of Sesame Oil. Biol Trace Elem Res 2022;200:3236-47. [Crossref] [PubMed]
97. Ge MH, Tian H, Mao L, et al. Zinc attenuates ferroptosis and promotes functional recovery in contusion spinal cord injury by activating Nrf2/GPX4 defense pathway. CNS Neurosci Ther 2021;27:1023-40. [Crossref] [PubMed]
98. Khatana C, Saini NK, Chakrabarti S, et al. Mechanistic Insights into the Oxidized Low-Density Lipoprotein-Induced Atherosclerosis. Oxid Med Cell Longev 2020;2020:5245308. [Crossref] [PubMed]
99. Shakoor H, Feehan J, Al Dhaheri AS, et al. Immune-boosting role of vitamins D, C, E, zinc, selenium and omega-3 fatty acids: Could they help against COVID-19? Maturitas 2021;143:1-9. [Crossref] [PubMed]
100. DiSilvestro RA, Dardenne M, Joseph E. Comparison of Thymulin Activity with Other Measures of Marginal Zinc Deficiency. Biol Trace Elem Res 2021;199:585-7. [Crossref] [PubMed]
101. Krone A, Fu Y, Schreiber S, et al. Ionic mitigation of CD4(+) T cell metabolic fitness, Th1 central nervous system autoimmunity and Th2 asthmatic airway inflammation by therapeutic zinc. Sci Rep 2022;12:1943. [Crossref] [PubMed]
102. Yin X, Chen S, Eisenbarth SC. Dendritic Cell Regulation of T Helper Cells. Annu Rev Immunol 2021;39:759-90. [Crossref] [PubMed]
103. Guo Z, Kasinathan D, Merriman C, et al. Cell-Surface Autoantibody Targets Zinc Transporter-8 (ZnT8) for In Vivo β-Cell Imaging and Islet-Specific Therapies. Diabetes 2023;72:184-95. [Crossref] [PubMed]
104. Ahmed NS, Lopes-Pires M, Pugh N. Zinc: an endogenous and exogenous regulator of platelet function during hemostasis and thrombosis. Platelets 2021;32:880-7. [Crossref] [PubMed]
105. Zhang J, Wieser A, Lin H, et al. Pretreatment with zinc protects Kupffer cells following administration of microbial products. Biomed Pharmacother 2020;127:110208. [Crossref] [PubMed]
106. Mammadova-Bach E, Braun A. Zinc Homeostasis in Platelet-Related Diseases. Int J Mol Sci 2019;20:5258. [Crossref] [PubMed]
107. Yang Y, Wang P, Guo J, et al. Zinc Overload Induces Damage to H9c2 Cardiomyocyte Through Mitochondrial Dysfunction and ROS-Mediated Mitophagy. Cardiovasc Toxicol 2023;23:388-405. [Crossref] [PubMed]
108. Ozyildirim S, Baltaci SB. Cardiovascular Diseases and Zinc. Biol Trace Elem Res 2023;201:1615-26. [Crossref] [PubMed]
109. Yang X, Chen S, Zhang S, et al. Intracellular zinc protects Kv7 K(+) channels from Ca(2+)/calmodulin-mediated inhibition. J Biol Chem 2023;299:102819. [Crossref] [PubMed]
110. Elgenidy A, Amin MA, Awad AK, et al. Serum Zinc Levels in Chronic Kidney Disease Patients, Hemodialysis Patients, and Healthy Controls: Systematic Review and Meta-Analysis. J Ren Nutr 2023;33:103-15. [Crossref] [PubMed]
111. Deng H, Liu Y, Shi Z, et al. Zinc regulates a specific subpopulation of VEGFA + microglia to improve the hypoxic microenvironment for functional recovery after spinal cord injury. Int Immunopharmacol 2023;125:111092. [Crossref] [PubMed]
112. Chen CM, Wu ML, Ho YC, et al. Exposure to Zinc Oxide Nanoparticles Disrupts Endothelial Tight and Adherens Junctions and Induces Pulmonary Inflammatory Cell Infiltration. Int J Mol Sci 2020;21:3437. [Crossref] [PubMed]
113. Kim JH, Jeong MS, Kim DY, et al. Zinc oxide nanoparticles induce lipoxygenase-mediated apoptosis and necrosis in human neuroblastoma SH-SY5Y cells. Neurochem Int 2015;90:204-14. [Crossref] [PubMed]
114. Qi Z, Zhou X, Dong W, et al. Neuronal Zinc Transporter ZnT3 Modulates Cerebral Ischemia-Induced Blood-Brain Barrier Disruption. Aging Dis 2023;15:2727-41. [Crossref] [PubMed]
115. Alhillawi ZH, Al-Hakeim HK, Moustafa SR, et al. Increased zinc and albumin but lowered copper in children with transfusion-dependent thalassemia. J Trace Elem Med Biol 2021;65:126713. [Crossref] [PubMed]
116. Malekahmadi M, Firouzi S, Rezayi M, et al. Association of Zinc and Copper Status with Cardiovascular Diseases and their Assessment Methods: A Review Study. Mini Rev Med Chem 2020;20:2067-78. [Crossref] [PubMed]
117. Kwon JH, Kim DK, Cho YE, et al. Zinc Action in Vascular Calcification. Prev Nutr Food Sci 2024;29:118-24. [Crossref] [PubMed]
118. Gao JW, Zhang SL, Hao QY, et al. Association of dietary zinc intake with coronary artery calcium progression: the Multi-Ethnic Study of Atherosclerosis (MESA). Eur J Nutr 2021;60:2759-67. [Crossref] [PubMed]
119. Yang X, Luo M, Jiang Y. The regulatory effect of zinc on the association between periodontitis and atherosclerotic cardiovascular disease: a cross-sectional study based on the National Health and Nutrition Examination Survey. BMC Oral Health 2024;24:703. [Crossref] [PubMed]
120. Li S, He RC, Wu SG, et al. LncRNA PSMB8-AS1 Instigates Vascular Inflammation to Aggravate Atherosclerosis. Circ Res 2024;134:60-80. [Crossref] [PubMed]
121. Khachigian LM. The MEK-ERK-Egr-1 axis and its regulation in cardiovascular disease. Vascul Pharmacol 2023;153:107232. [Crossref] [PubMed]
122. Chen F, Ning Y, Liu J, et al. miR-147a targets ZEB2 to regulate ox-LDL-induced monocyte adherence to HUVECs, atherosclerotic plaque formation, and stability in atherosclerosis. J Biol Chem 2023;299:104657. [Crossref] [PubMed]
123. Samah N, Ugusman A, Hamid AA, et al. Role of Matrix Metalloproteinase-2 in the Development of Atherosclerosis among Patients with Coronary Artery Disease. Mediators Inflamm 2023;2023:9715114. [Crossref] [PubMed]
124. Perpétuo L, Barros AS, Dalsuco J, et al. Coronary Artery Disease and Aortic Valve Stenosis: A Urine Proteomics Study. Int J Mol Sci 2022;23:13579. [Crossref] [PubMed]
125. Langsted A, Nordestgaard BG, Benn M, et al. PCSK9 R46L Loss-of-Function Mutation Reduces Lipoprotein(a), LDL Cholesterol, and Risk of Aortic Valve Stenosis. J Clin Endocrinol Metab 2016;101:3281-7. [Crossref] [PubMed]
126. Geach T. Genetics. APOC3 mutations lower CVD risk. Nat Rev Cardiol 2014;11:496. [Crossref] [PubMed]
127. Tontonoz P, Wu X, Jones M, et al. Long Noncoding RNA Facilitated Gene Therapy Reduces Atherosclerosis in a Murine Model of Familial Hypercholesterolemia. Circulation 2017;136:776-8. [Crossref] [PubMed]
128. Michael DR, Ashlin TG, Buckley ML, et al. Liver X receptors, atherosclerosis and inflammation. Curr Atheroscler Rep 2012;14:284-93. [Crossref] [PubMed]
129. Lin J, Kakkar V, Lu X. Impact of MCP-1 in atherosclerosis. Curr Pharm Des 2014;20:4580-8. [Crossref] [PubMed]
130. Zhao J, Cheng Z, Quan X, et al. Dimethyl fumarate protects cardiomyocytes against oxygen-glucose deprivation/reperfusion (OGD/R)-induced inflammatory response and damages via inhibition of Egr-1. Int Immunopharmacol 2020;86:106733. [Crossref] [PubMed]
131. Momi S, Falcinelli E, Petito E, et al. Matrix metalloproteinase-2 on activated platelets triggers endothelial PAR-1 initiating atherosclerosis. Eur Heart J 2022;43:504-14. [Crossref] [PubMed]
132. Takagishi T, Hara T, Fukada T. Recent Advances in the Role of SLC39A/ZIP Zinc Transporters In Vivo. Int J Mol Sci 2017;18:2708. [Crossref] [PubMed]
133. Du L, Zhang H, Zhao H, et al. The critical role of the zinc transporter Zip2 (SLC39A2) in ischemia/reperfusion injury in mouse hearts. J Mol Cell Cardiol 2019;132:136-45. [Crossref] [PubMed]
134. Zhang H, Yang N, He H, et al. The zinc transporter ZIP7 (Slc39a7) controls myocardial reperfusion injury by regulating mitophagy. Basic Res Cardiol 2021;116:54. [Crossref] [PubMed]
135. Aierken Y, He H, Li R, et al. Inhibition of Slc39a14/Slc39a8 reduce vascular calcification via alleviating iron overload induced ferroptosis in vascular smooth muscle cells. Cardiovasc Diabetol 2024;23:186. [Crossref] [PubMed]
136. Wang J, Cheng X, Zhao H, et al. Downregulation of the zinc transporter SLC39A13 (ZIP13) is responsible for the activation of CaMKII at reperfusion and leads to myocardial ischemia/reperfusion injury in mouse hearts. J Mol Cell Cardiol 2021;152:69-79. [Crossref] [PubMed]
137. Josefs T, Boon RA. The Long Non-coding Road to Atherosclerosis. Curr Atheroscler Rep 2020;22:55. [Crossref] [PubMed]
138. Im SS, Osborne TF. Liver x receptors in atherosclerosis and inflammation. Circ Res 2011;108:996-1001. [Crossref] [PubMed]
139. Duan M, Li T, Liu B, et al. Zinc nutrition and dietary zinc supplements. Crit Rev Food Sci Nutr 2023;63:1277-92. [Crossref] [PubMed]
140. Lassi ZS, Haider BA, Bhutta ZA. Zinc supplementation for the prevention of pneumonia in children aged 2 months to 59 months. Cochrane Database Syst Rev 2010;CD005978. [PubMed]
141. Shi Y, Hao R, Ji H, et al. Dietary zinc supplements: beneficial health effects and application in food, medicine and animals. J Sci Food Agric 2024;104:5660-74. [Crossref] [PubMed]
142. Praharaj S, Skalicky M, Maitra S, et al. Zinc Biofortification in Food Crops Could Alleviate the Zinc Malnutrition in Human Health. Molecules 2021;26:3509. [Crossref] [PubMed]
143. Lowe NM, Gupta S. Food fortification programmes and zinc deficiency. Nat Food 2024;5:546-7. [Crossref] [PubMed]