Context-specific effects of CCM2 on atherosclerosis

Genetic variants in the Cerebral Cavernous Malformation 2 (CCM2) locus are associated with coronary artery disease (CAD), but the role of CCM2 in atherosclerosis is unknown. We previously identified CCM2 through endothelial cell (EC) Perturb-seq as a regulator of transcriptional programs enriched for CAD risk genes, and predicted that reduced CCM2 function would be athero-protective. Here, we integrated human genetics, functional studies in human aortic ECs, and single cell profiling with mouse models of atherosclerosis to define the effects of reduced CCM2 signaling across disease stages. Ccm

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