Zinc deficiency and cellular oxidative stress: prognostic implications in cardiovascular diseases

Abstract

Zinc is an essential nutrient for human health and has anti-oxidative stress and anti-inflammatory functions. The association between zinc deficiency and the development of cardiovascular diseases (CVDs) has been supported by numerous studies. Supplementing zinc can reduce the risk of atherosclerosis and protect against myocardial infarction and ischemia/reperfusion injury. In this review we summarize the evidence in the literature, to consolidate the current knowledge on the dysregulation of zinc homeostasis in CVDs, and to explore the significant roles of the zinc homeostasis-regulatory proteins in cardiac physiology and pathophysiology. Moreover, this review also deliberates on the potential diagnostic and prognostic implications of zinc/zinc homeostasis-associated molecules (ZIP, ZnT, and MTs) in CVDs.

Keywords: Irt-like protein (ZIP); ROS; Zrt; atherosclerosis; cardiovascular diseases; inflammation; metallothionein (MT); zinc homeostasis; zinc transporter (ZnT).

Figure 1

Expression levels of zinc transporters and MTs in heart and vascular cells. Data are extracted from publically available RNA-seq databases. (A) ZIPs, ZnTs, and MTs expression in human heart muscle tissue. Each gene's reads per kilobase per million reads placed (RPKM) was downloaded and examined for normal heart tissues. Error bars represent a standard deviation from RPKM values in four tissue samples. (B) ZIPs, ZnTs, and MTs expression in human endothelial cell lines. Transcript Per Million (TPM) of each gene was searched in RNA-seq data in Cell atlas section in Human Protein Atlas. Two bars in each gene represent HUVEC TERT2 (blue) and TIME cells (orange), respectively. (C) ZIPs, ZnTs, and MTs expression in human bronchial smooth muscle cells. Fragments per kilobase of transcript per million mapped reads (FPKM) value for each gene was obtained from the “Control Baseline” group in dataset GSE58434 at the Gene Expression Omnibus.

Figure 2

Schematic summary of key regulatory roles of zinc in CVDs. ZIPs and ZnTs are simply depicted to be localized in the cell plasma membrane and intracellular organelle membrane. MTs represents metallothionein proteins.