Rho kinase inhibitors as potential therapeutic agents for cardiovascular diseases.
RhoA and Rho-kinase (ROCK) participate in diverse cellular signaling functions such as smooth muscle contraction, cytoskeleton rearrangement, and cell migration and proliferation. In smooth muscle, ROCK plays an important role in calcium sensitization, an event that controls vascular vessel tone. Recent studies using ROCK inhibitors along with cellular and molecular biology techniques have revealed a pivotal role of this enzyme in many other aspects of cardiovascular function. This review will focus on the current understanding of Rho/ROCK signaling pathways and discuss the use of ROCK inhibitors as therapeutic agents for cardiovascular diseases ranging from hypertension to atherosclerosis.
Departments of Vascular Biology and Medicinal, GlaxoSmithKline Pharmaceuticals, 709 Swedeland Road, King of Prussia, PA 19406, USA. Erding_Hu-1@gsk.com
Erding
E
Hu
Dennis
D
Lee
D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D015394:Molecular Structure; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000201:enzymology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D054460:rho-Associated Kinases
D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases