Advanced atherosclerotic plaques display extensive DNA damage, seen in VSMCs, macrophages, endothelial cells, and in circulating cells, and in both nuclei and mitochondria. DNA damage can reflect both ongoing damage-inducing stimuli and defects in the repair machinery. Recent work has shown that DNA damage induces VSMC death and senescence, increases monocyte pro-inflammatory cytokine release, promoting both atherosclerosis and plaque vulnerability. We are investigating the role of oxidative damage in atherosclerosis and the mechanisms involved using both primary human and mouse VSMCs in vitro and conditional transgenic in vivo models of atherosclerosis.
DNA damage ; vascular smooth muscle cells (VSMC) ; senescence ; apoptosis ; atherosclerosis
Controlling Inflammation Through DNA Damage and Repair. Shah A, Bennett M. Circ Res. 2016 Sep 2;119(6):698-700.