PHACTR1, a coronary artery disease risk gene, drives endothelial dysfunction

Recent genome-wide association studies have identified PHACTR1 as a critical risk gene associated with polyvascular diseases. However, it remains elusive how PHACTR1 is involved in endothelial dysfunction. Here, we show that PHACTR1 triggers endothelial inflammation by activating NF-κB and disrupts Nitric oxide production by inhibiting Akt/eNOS activation to induce endothelial diastolic disorder. Whereas, Atorvastatin particularly plays an inhibitory effect on PHACTR1 gene expression in a dose-dependent manner among PHACTR family in endothelial cells. PHACTR1 may interact with PP1 with coupling with heat shock protein 8 (HSPA8) to dephosphorylate Akt or eNOS.