Polycomb Repressive Complex 2 drives flow-sensitive endothelial states underlying vascular inflammation and disease

Here, we identify, Polycomb Repressive Complex (PRC) 2 as a potent, therapeutically targetable determinant of vascular inflammation and ASCVD progression. PRC2 is an enzyme complex that trimethylates Histone H3 Lysine27 (H3K27me3) in gene promoter/enhancers to block gene transcription.

Integrated experimental and mechanistic computational studies identified PRC2 as a central determinant of the endothelial cell state transition to an inflammatory state. PRC2 maintains the endothelial pro-inflammatory state by direct suppression of Klf2/4 transcription. PRC2 activity is elevated in endothelium from human ASCVD lesions.