Abstrait

Deoxyribonucleic acid repair in atherosclerotic coronary artery disease

Gilpin TR, Gabara L, Miles EA, Curzen NP, Mahmoudi M

Despite recent advances in the therapeutic and interventional treatment of coronary artery disease the global prevalence of this disease is increasing and the associated mortality and morbidity remain high. Alongside well-established risk factors such as smoking, hypertension, hypercholesterolaemia and diabetes mellitus, deoxyribonucleic acid (DNA) damage, cascade protein signalling and the associated repair pathways are becoming increasingly recognised as major causative co-factors in the pathogenesis of atherosclerosis. A number of in vitro studies have shown defective DNA repair is instrumental in the pathogenesis and progression of atherosclerotic plaques with a positive correlation observed between the level of DNA damage and the severity of the atherosclerotic lesions. In knockdown mouse models of atherosclerosis, the DNA repair signalling cascade has been shown to be amenable to pharmacological manipulation and overexpression of specific repair proteins attenuate atherogenesis. However, to date there is little in-human data which supports these findings. This review will explore the current evidence and understanding of the role of DNA damage and repair in the pathogenesis of atherosclerosis and address possible therapeutic interventions for treatment.