Pathophysiology and Molecular Mechanisms of Coronary Artery Spasm

Rho-kinase plays a central role in the pathogenesis of coronary artery spasm caused by vascular smooth muscle cell (VSMC) hypercontraction. Rho-kinase belongs to the family of serine/threonine kinases and is an important downstream effector of the small GTP-binding protein RhoA. Two isoforms of Rho-kinase, ROCK1 and ROCK2, have different functions with ROCK1 for circulating inflammatory cells and ROCK2 for vascular smooth muscle cells. The RhoA/Rho-kinase pathway plays an important role in many cellular functions, including contraction, motility, proliferation, and apoptosis, leading to the development of cardiovascular diseases. In addition to vasospasm, important roles of Rho-kinase in vivo have been demonstrated in the pathogenesis of arteriosclerosis, ischemia/reperfusion injury, hypertension, pulmonary hypertension, stroke, and heart failure. Furthermore, the beneficial effects of fasudil, a selective Rho-kinase inhibitor, have been demonstrated for the treatment of several cardiovascular diseases in animals and humans. Thus, the Rho-kinase pathway is an important new therapeutic target in vasospasm and other cardiovascular diseases.