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The important role of histone deacetylases in modulating vascular physiology and arteriosclerosis

      Highlights

      • Histone deacetylases play a key role in modulating the function of endothelial cells.
      • Histone deacetylases regulate the proliferation and growth of vascular cells.
      • Histone deacetylases contribute significantly to the development of atherosclerosis.

      Abstract

      Cardiovascular diseases are the leading cause of deaths in the world. Endothelial dysfunction followed by inflammation of the vessel wall leads to atherosclerotic lesion formation that causes ischemic heart and myocardial hypertrophy, which ultimately progress into cardiac dysfunction and failure. Histone deacetylases (HDACs) have been recognized to play crucial roles in cardiovascular disease, particularly in the epigenetic regulation of gene transcription in response to a variety of stresses. The unique nature of HDAC regulation includes that HDACs form a complex co-regulatory network with other transcription factors, deacetylate histones and non-histone proteins to facilitate the regulatory mechanism of the vascular system. The selective HDAC inhibitors are considered as the most promising target in cardiovascular disease, especially for preventing cardiac hypertrophy. In this review, we discuss our present knowledge of the cellular and molecular basis of HDACs in mediating the biological function of vascular cells and related pharmacologic interventions in vascular disease.

      Graphical abstract

      Keywords

      Abbreviations:

      CVD (cardiovascular disease), HDAC (histone deacetylase), HAT (histone acetyltransferases), Sir (silent information regulator), ROS (reactive oxygen species), HUVEC (human umbilical vein endothelial cells), PP2A (protein phosphatase 2A), MEF2 (myocardial enhancing factor 2), VEGF (vascular endothelial growth factor), HIF (hypoxia-inducible factor), PDK1 (protein kinase D1), VSMC (vascular smooth muscle cells), IGF1R (insulin-like growth factor 1 receptor), TBP (TATA-binding protein), SMC (smooth muscle cell), PDGF (platelet-derived growth factor), CaMKII (Ca2+/calmodulin-dependent protein kinase II), Arg2 (Arginase 2), oxLDL (oxidized low-density lipoproteins), CIITA (major histocompatibility class II transactivator), IFN-gamma (interferon gamma)
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