Role of DNA damage in cardiovascular disease.

Patients with some progeroid syndromes, such as Werner syndrome, exhibit atherosclerotic cardiovascular disease (CVD) at a young age as a manifestation of premature aging. Recent studies have revealed that most progeroid syndromes are caused by genetic defects in specific molecules involved in the DNA damage response, a cornerstone of genome stability. Ionizing radiation is one of the most potent genotoxic stimuli and causes various kinds of DNA damage. Further, there is increasing evidence that therapeutic radiation treatments can cause cardiovascular complications. Here, we describe the DNA damage and subsequent response, review recent advances in the understanding of the molecular basis of progeroid syndromes (especially those syndromes that involve CVD), review the pathological and epidemiological analysis of radiation-induced CVD, and discuss the possible role of DNA damage and the DNA damage response in the pathogenesis of atherosclerotic CVD.