Rho kinase: an important mediator of atherosclerosis and vascular disease.
Atherosclerosis is a complex inflammatory process characterized by the cross-talk between excessive inflammation and lipid accumulation. In the past few years, compelling evidence suggests that statins can decrease vascular inflammation and attenuate the development of atherosclerosis through their so-called "pleiotropic effects". These cholesterol-independent effects are predominantly due to their ability to inhibit isoprenoid synthesis. In particular, inhibition of geranylgeranylpyrophosphate synthesis leads to inhibition of Rho and its downstream target, Rho-kinase (ROCK). Thus, one of the beneficial effects of statin therapy could be due to inhibitory effects on ROCK. ROCK is involved in mediating diverse cellular functions such as smooth muscle contraction, cell migration and proliferation. While increased ROCK activity is associated with endothelial dysfunction, cerebral ischemia, coronary vasospasms and metabolic syndrome, the inhibition of ROCK by statins or selective ROCK inhibitors leads to up-regulation of endothelial nitric oxide synthase (eNOS), decreased vascular inflammation, and reduced atherosclerotic plaque formation. This review will focus on the impact of ROCK in cardiovascular disease and its contributory role to vascular inflammation and the atherosclerosis.
Zhou
Qian
Q
Vascular Medicine Research Unit, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Liao
James K
JK
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D050197:Atherosclerosis / Q000188:drug therapy / Q000201:enzymology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy / Q000201:enzymology*; D050356:Lipid Metabolism / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D047428:Protein Kinase Inhibitors; D054460:rho-Associated Kinases