Can the DNA damage response be harnessed to modulate atherosclerotic plaque phenotype?

Abstract

<i>Gray et al</i> describe studies to examine smooth muscle cell (SMC)-selective effects of acceleration or inhibition of double-strand DNA break repair on atherosclerotic lesion phenotype in the ApoE-/- mouse model. Markers of the DNA damage response (DDR) and expression of DNA repair enzymes are both significantly elevated in human atherosclerotic plaques as compared with non-atherosclerotic mammary arteries, and are also increased in experimental models of atherosclerosis, a process that can be reversed by dietary lipid lowering. The report by <i>Gray et al</i> provides important insights into the specific contribution of SMCs to plaque phenotype when the DDR is manipulated <i>in vivo</i>. While complementary analyses of double-strand DNA break repair in other major cell types within atherosclerotic lesions are needed, data from the studies by <i>Gray et al</i> suggest the possibility of harnessing atheroprotective features of the ataxia telangiectasia mutated (ATM) kinase,^, a primary initiator of the DDR.