Abstract
Atherosclerosis (AS), the most common underlying pathology for coronary artery disease, is a chronic inflammatory, proliferative disease in large- and medium-sized arteries. The vascular endothelium is important for maintaining vascular health. Endothelial dysfunction is a critical early event leading to AS, which is a major risk factor for stroke and myocardial infarction. Accumulating evidence has suggested the critical roles of histone deacetylases (HDACs) in regulating vascular cell homeostasis and AS. The purpose of this review is to present an updated view on the roles of HDACs (Class I, Class II, Class IV) and HDAC inhibitors in vascular dysfunction and AS. We also elaborate on the novel therapeutic targets and agents in atherosclerotic cardiovascular diseases.
Highlights
Atherosclerosis (AS) is the critical underlying pathology of cardiovascular disease (CVD), which ranks the first on the morbidity and mortality of diseases (Fanelli et al, 2017; Libby et al, 2019; Niu et al, 2019; Wang et al, 2019)
It was found that insulin-like growth factor 1 (IGF-1) enhanced the phosphorylation of HDAC5 that is associated with AS and led to nuclear export of HDAC5, which was mediated by Nox4-dependent reactive oxygen species (ROS) production, as well as the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathways (Pietruczuk et al, 2019)
Rossig et al (2005) found that inhibition of histone deacetylases (HDACs) abolished the endothelial differentiation from adult progenitor cells by inhibiting the expression of homeobox transcription factors homeobox A9 (HoxA9), which is a regulator of endothelial nitric oxide (NO) synthase (eNOS), vascular endothelial growth factor (VEGF)-R2, VE-cadherin, and endothelial cells (ECs) maturation induced by shear stress
Summary
Atherosclerosis (AS) is the critical underlying pathology of CVD, which ranks the first on the morbidity and mortality of diseases (Fanelli et al, 2017; Libby et al, 2019; Niu et al, 2019; Wang et al, 2019) It lessens the elasticity of the arteries and may lead to myocardial infraction, ischemic stroke, cerebrovascular incidents, and peripheral vascular disease (Ziegler et al, 2019). The healthy endothelium is important to maintain vascular homeostasis It possesses the function of generating bioactive NO, regulating vascular tone, protecting the endothelial cell (EC) integrity, Role of HDAC in Atherosclerosis repairing the injury and inducing angiogenesis (Huynh and Heo, 2019).
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