title: Striking crosstalk of ROCK signaling with endothelial function.
abstract: Rho-associated coiled-coil forming protein kinases (ROCKs), the downstream target proteins of RhoA, are ubiquitously expressed serine-threonine protein kinases. ROCKs have diverse cellular functions, e.g. smooth muscle contraction, actin cytoskeleton organization, cell adhesion, and gene expression. Accumulating evidence has revealed that ROCKs are substantially involved in cardiovascular disorders such as angina, cerebral ischemia, myocardial ischemia, and cardiac hypertrophy. So far, the significant relationship of ROCKs with endothelial function has been reported. ROCKs inhibition by statins or other selective inhibitors leads to the upregulation and activation of endothelial nitric oxide synthase, resulting in the reduction of vascular inflammation and atherosclerosis. Meanwhile, it has been also demonstrated that endogenous nitric oxide could inhibit RhoA/ROCK signaling pathway. Taken together, there might be critical crosstalk of ROCKs with endothelial function. In addition, we further focus on leukocyte ROCK activity as a surrogate marker in patients with atherosclerosis-related diseases. Indeed, leukocyte ROCK activity has been shown to be increased in atherosclerotic patients, indicating the possible usage of leukocyte ROCK activity as a surrogate marker similar to endothelial function evaluated by flow-mediated dilation. Here, we review concerning ROCK signaling pathway, especially focusing on the crosstalk of ROCKs with endothelial function.
authors.affiliation: Department of Cardiovascular Regeneration and Medicine, Research Center for Radiation Genome Medicine, Research Institute for Radiation Biology and Medicine (RIRBM), Hiroshima University, Japan. knoma@hiroshima-u.ac.jp
authors.forename: Kensuke
authors.initials: K
authors.lastname: Noma
authors.forename: Yasuki
authors.initials: Y
authors.lastname: Kihara
authors.forename: Yukihito
authors.initials: Y
authors.lastname: Higashi
mesh_terms: D050197:Atherosclerosis / Q000378:metabolism; D042783:Endothelial Cells / Q000502:physiology*; D006801:Humans; D020239:Receptor Cross-Talk / Q000502:physiology*; D015398:Signal Transduction; D054460:rho-Associated Kinases / Q000502:physiology*
chemical_list: D054460:rho-Associated Kinases