Insights into the Pathogenesis and Intervention of Atherosclerosis

Emerging Epigenetic Therapy for Vascular Proliferative Diseases

“…Moreover, cell cycle is the final common pathway where all the growth regulatory signals converge, and thus, makes a rational target of antiproliferative therapeutics to inhibit vascular proliferative diseases. Some of the experimental studies indeed reveal that inhibition of cell cycle progression emerges as an important therapeutic target for prevention of vascular proliferative diseases (Dzau et al, 2002;Ranganna et al, 2006;Von der Leyen & Dzau, 2001). Different approaches such as pharmacological agents, irradiation, and gene therapy have been used for arresting VSMC proliferation.…”

“…In spite of the substantial understanding of the etiology and the clinical management of these vascular proliferative diseases, they are still life threatening diseases and reasons are not fully evident. Based on the recent finding of the role of epigenetics in human diseases, it is proper to expect that epigenetic mechanisms enforces an additional layer of gene regulation that alters chromatin structure, and dynamics in the pathogenesis of vascular proliferative diseases (Ekstrom, 2009;Pons et al, 2009;Ranganna et al, 2006;Turunen, 2009). Epigenetic mechanisms are essential for the functioning of genomes to regulate normal development and maintenance of organisms, and to facilitate their interaction with surrounding environment.…”

“…These include, DNA methylation, histone posttranslational modifications and non-coding RNA (ncRNA) expression based mechanisms, each of these mechanisms is essential for regulation of gene expression. Therefore, it is anticipated that the genetic and environmental factors that are relevant to the development of vascular proliferative diseases by their effect on inflammation, VSMC proliferation and vessel remodeling, is regulated by epigenetic mechanisms through the modification of chromatin structure, dynamics and accessibility (Ekstrom, 2009;Pons et al, 2009;Ranganna et al, 2006;Turunen, 2009). Although there is an outbreak of interest and enthusiasm in linking altered epigenetic mechanisms to human pathologies particularly cancers, it is relatively unexplored area regarding cardiovascular diseases.…”

“…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.…”