Environmental exposures, epigenetics and cardiovascular disease

Abstract

Purpose of review: Epigenetic modifications are heritable alterations of the genome, which can govern gene expression without altering the DNA sequence. The purpose of this review is to render an overview of the possible mechanisms of epigenetic regulation of gene expression in response to environmental pollutants leading to cardiovascular diseases (CVD).

Recent findings: An era of cataloging epigenetic marks of the various diseased states has recently commenced, including those within the genes responsible for atherosclerosis, ischemia, hypertension and heart failure. From varied study approaches directed either toward the general understanding of the key pathway regulatory genes, or sampling population cohorts for global and gene-specific changes, it has been possible to identify several epigenetic signatures of environmental exposure relevant to CVD. Signatures of epigenetic dysregulation can be detected in peripheral blood samples, even within a few hours of environmental exposure. However, the field now faces the demand for thorough, systematic, rationalized approaches to establish the relation of exposure-driven epigenetic changes to clinical outcomes, by using sophisticated and reliable research designs and tools.

Summary: An understanding of chromatin remodelling in response to environmental stimuli conducive to CVD is emerging, with the promise of novel diagnostic and therapeutic candidates.

Figure 1

Epigenetic modifications of the nucleosomal histones and DNA, regulating gene expression. Histone modifications of compactly coiled heterochromatic regions, or relaxed transcriptionally active chromatin. H, histone; K, lysine; me, methylation; me3, trimethylation; ac, acetylation; DNA methylation silencing the gene; ^meCpG, methylated Cytosine in Cytosine-Guanine dinucleotide sequences within the DNA.

Figure 2

Mechanism of environmental exposure mediated cardiovascular outcome. A. Air pollution induces release of cytokines and chemokines, causing inflammatory cellular recruitment and local inflammation and cyclical systemic impact through the vasculature. B. Inflammatory and oxidative stress induces atherosclerotic processes. Ingestion of particulate matter activates macrophages, induces reactive oxygen species, monocyte adhesion molecules and accumulation of monocytes on endothelial layer, foam cell transformation. Subsequently, endothelial cell dysfunction and smooth muscle cell proliferation take place. TNF, tumor necrosis factor; iNOS, inducible nitric oxide synthase; NO-, nitric oxide, O₂-, superoxide; ONOO-, peroxynitrile; ICAM-1 Intercellular adhesion molecule 1; VCAM-1, Vascular cell adhesion molecule 1; eNOS, endothelial nitric oxide synthase. C. Exposure to environmental pollutants causes oxidative stress and inflammation, which triggers onset of, or exacerbates cardiovascular disease process at any stage of progression.