**2.3 Epigenetic enzymes implicated in cardiovascular diseases**

Cardiovascular disease, one of the leading causes of mortality globally, is comprised of a group of diverse disorders known to be influenced by genetic, environmental, and epigenetic mechanisms [68]. For example, GWAS on atherosclerotic aorta versus normal aorta showed the differential methylation of DNA is associated with atherosclerotic plaque stability, vascular remodeling, low-density lipoprotein (LDL) signaling, among other biological processes [69]. This suggests the role of altered DNA methylation in the pathogenesis of atherosclerosis. Similarly, casecontrol investigations on heart failure patients revealed differential methylation of angiogenic genes known to be involved in endothelial cell migration and capillary tube formation [70]. Also, multiple studies have demonstrated that high levels of HDAC and DNA/histone methylation have been linked to the causation of high blood pressure, a known symptom of hypertension [71]. Similarly, the use of HDAC inhibitors attenuates myocardial infarction in *in vivo* studies [72]. A separate study showed that environmental factors, such as particulate matter in air pollution known to cause impaired cardiac function, increase the methylation of Toll-like receptor 2 (TLR2), causing its gene silencing. TLR2 is known to proffer immunity following environmental challenges [73]. Thus, its hypermethylation has been linked to the cardiac dysfunction caused by air pollution. Also, *de novo* mutations have been found in histone-modifying genes in congenital heart disease, including KMT2D, KDM5A, and KDM5B, thereby suggesting their role in the disruption of cardiac development [74]. The overexpression of PRMT6 has been reported to induce cardiac hypertrophy and its associating increase in asymmetric dimethylation of H3R2 promotes the expression of atrial natriuretic peptide (ANP), a hypertrophic marker [75]. This diverse implication of epigenetic enzymes in various cardiac functions suggests its potential as a treatment approach for cardiovascular diseases.
