DNA Damage and Repair in Atherosclerosis: Current Insights and Future Perspectives

Abstract

Atherosclerosis is the leading cause of morbidity and mortality among Western populations. Over the past two decades, considerable evidence has supported a crucial role for DNA damage in the development and progression of atherosclerosis. These findings support the concept that the prolonged exposure to risk factors (e.g., dyslipidemia, smoking and diabetes mellitus) leading to reactive oxygen species are major stimuli for DNA damage within the plaque. Genomic instability at the cellular level can directly affect vascular function, leading to cell cycle arrest, apoptosis and premature vascular senescence. The purpose of this paper is to review current knowledge on the role of DNA damage and DNA repair systems in atherosclerosis, as well as to discuss the cellular response to DNA damage in order to shed light on possible strategies for prevention and treatment.

Up-regulation of MSH2, XRCC1 and ATM genes in patients with type 2 diabetes and coronary artery disease

“…Recent mutation theory of atherosclerosis has provided new insights into the role of DNA damages in the pathogenesis of CAD [17,18]. Although several DNA damages have already been detected in endothelial, smooth muscle cell, and PBMCs of CAD patients, the question as to how CAD alters the expression of DNA repair genes remains unanswered [19]. To the best of our knowledge, this study is the first to compare the mRNA expression of ATM, XRCC1, and MSH2 genes in T2DM patients with CAD versus CADÀ ones.…”

APE1/Ref-1 as an emerging therapeutic target for various human diseases: phytochemical modulation of its functions

“…176 During 2008, 244 deaths were recorded because of CVD per 10 000 individuals according to a report published by the American Heart Association. 177 Hypertension affects >50 million Americans and 65% of people older than 65 years.…”

Proprotein convertase furin/PCSK3 and atherosclerosis: New insights and potential therapeutic targets

“…The pathogenesis of atherosclerosis or atherogenesis is closely associated with many risk factors, including smoking, obesity, inflammatory response, type 2 diabetes mellitus (T2D), dyslipidemia, cell cycle progression and hypertension [1]. Atherosclerotic lesions result from the interaction of different chemokines and cytokines with diverse non-vascular and vascular cell types, such as vascular smooth muscle cells (VSMCs), endothelial cells (ECs), thrombocytes and mononuclear inflammatory cells (MNCs) [2].…”