Macrophage NCOR1 protects from atherosclerosis by repressing a pro-atherogenic PPARγ signature

Macrophage NCOR1 protects from atherosclerosis by repressing a pro-atherogenic PPARγ signature. Eur Heart J, DOI 10.1093/eurheartj/ehz667

The development of atherosclerosis is triggered by inflammatory and metabolic cues, whose downstream pathways are connected in immunometabolic networks that are regulated by key transcriptional coregulators, such as nuclear receptor corepressor 1 (NCOR1). This study demonstrates that macrophage NCOR1 represses pro-atherogenic functions of proliferator-activated receptor gamma (PPARγ). Consistently, the deletion of macrophage Ncor1 aggravates atherosclerosis in mice. Moreover, analyses of human carotid plaque specimens suggest that the NCOR1-driven PPARγ suppression is also protective in human plaque development and vulnerability. Therefore, the defined function of macrophage NCOR1 in atherosclerosis may open new therapeutic strategies to prevent the development and progression of the atherosclerosis and cardiovascular disease.