Journal of Vascular Medicine & Surgery

Abstract

Rock the Rock of Atherosclerosis

Suowen Xu

The Rho-Associated Coiled-Coil Containing Protein Kinase (ROCK1 and ROCK2) were one of the downstream effectors of the small GTPase Rho. The Rho/ROCK pathway plays an important role in mediating multiple cellular processes, including endothelial dysfunction, the proliferation and migration of smooth muscle cells, foam cell formation, and arterial stiffness and aging, all of which are involved in the pathogenesis of atherosclerosis. Vascular cells (including endothelial cells, smooth muscle cells, and macrophages) undergo pathophysiological changes through the ROCK signaling pathway and ROCK inhibitors are being developed as effective therapeutic agents for atherosclerotic cardiovascular diseases. However, it is not entirely clear how ROCK isoforms are regulated, and how both isoforms contribute to the pathogenesis of atherosclerosis. A recent article from Liao’s laboratory demonstrated that deletion of the ROCK2 allele in BM-derived cells attenuates plaque formation in cholesterol-fed LDLr-/- mice. Mechanistically, ROCK2 deletion decreases foam cell formation (the hallmark of atherosclerosis) by facilitating Reverse Cholesterol Transport (RCT) in macrophages, through peroxisome proliferator-activated receptor-γ/liver X receptor-α/ATP-binding cassette transporter A1 pathway. This study provides further mechanistic insight into the therapeutic benefits of ROCK2 inhibition in preventing the development of atherosclerosis.