Epigenetic histone acetylation modifiers in vascular remodelling – new targets for therapy in cardiovascular disease

Emerging Epigenetic Therapy for Vascular Proliferative Diseases

“…Atherosclerosis and restenosis both are multifactorial vascular occlusive processes but exhibit certain similarities and differences in the origin and progression of their development (Dzau et al, 2002;Pons et al, 2009). Inflammatory response of activated endothelial cells to injury or insults elicits both these processes.…”

“…Although they share some of the risk factors such as hypertension and diabetes, there is a consensus that atherosclerosis develops in response to elevated low-density lipoproteins (LDL) and cigarette smoke. On the other hand, VSMC proliferation is the primary pathophysiological mechanism in restenosis, which is largely due to transcending wound healing response to clinical procedures such as balloon angioplasty, stent placement and vein graft surgery [Dzau et al, 2002;Pons et al, 2009]. While restenosis appears to be insensitive to circulating lipids, accumulation of oxidized LDL is the characteristic feature of atherosclerosis.…”

“…Remodeling of the injured vessel, proliferation and migration of vascular smooth muscle cells (VSMC) and elaboration and accumulation of extracellular matrix proteins are main traits of these diseases (Dzau et al, 2002;Libby, 2002;Pons et al, 2009;Ranganna et al, 2006;Ross, 1995;). Despite the substantial progress in understanding the etiology and the clinical management of atherosclerosis and restenosis, they are still life threatening diseases.…”

“…Different cell types; distinct cellular pathways and processes; and multiple genes within each participating cell types that are vulnerable to both genetic and environmental risk factors participate in the pathogenesis of atherosclerosis and restenosis. Recently, it is recognized that besides the genetic control epigenetic mechanisms regulate development and maintenance of organisms or their interaction with surrounding environment through the coordination of a set of reversible modifications that turn parts of the genome 'off' and 'on' at strategic times and at specific sites causing changes in gene expression with no changes in DNA sequences (Ekstrom, 2009;Pons et al, 2009;Ranganna et al, 2006;Turunen, 2009). The two well-known epigenetic mechanisms, DNA methylation and histone modifications change the chromatin structure and dynamics that alter gene functions by influencing gene expressions.…”

An Epigenome-Wide Association Study of Inflammatory Response to Fenofibrate in the Genetics of Lipid Lowering Drugs and Diet Network

“…Since these alterations in chromatin structure are reversible, these epigenetic modifications can be subjected to pharmacological intervention for the management of cardiovascular diseases [57]. Plaques preferentially develop in arterial regions of disturbed blood flow (d-flow), thus altering endothelial gene expression and function.…”