DNA damage response, a double-edged sword for vascular aging

Vascular aging is a major risk factor for age-related cardiovascular diseases, which have high rates of morbidity and mortality. It is characterized by changes in the blood vessels, such as macroscopically increased vascular diameter and intima-medial thickness, chronic inflammation, vascular calcification, arterial stiffening, and atherosclerosis. DNA damage and the subsequent various DNA damage response (DDR) pathways are important causative factors of vascular aging. Deficient DDR, which may result in the accumulation of unrepaired damaged DNA or mutations, can lead to vascular aging. On the other hand, over-activation of some DDR proteins, such as poly (ADP ribose) polymerase (PARP) and ataxia telangiectasia mutated (ATM), also can enhance the process of vascular aging, suggesting that DDR can have both positive and negative effects on vascular aging. Despite the evidence reviewed in this paper, the role of DDR in vascular aging and potential therapeutic targets remain poorly understood and require further investigation.