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

Gray et al 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 Gray et al provides important insights into the specific contribution of SMCs to plaque phenotype when the DDR is manipulated in vivo. While complementary analyses of double-strand DNA break repair in other major cell types within atherosclerotic lesions are needed, data from the studies by Gray et al suggest the possibility of harnessing atheroprotective features of the ataxia telangiectasia mutated (ATM) kinase,, a primary initiator of the DDR.