Targeting Rho and Rho-kinase in the treatment of cardiovascular disease.
The small GTPase Rho and its downstream effector Rho-kinase contribute to agonist-induced vascular contraction via Ca2+ sensitization. Reasonably selective pharmacological inhibitors of these proteins have been developed and are now widely used experimentally to investigate the role of this signaling pathway in vascular function. Rho and Rho-kinase have attracted increasing clinical interest as a result of emerging evidence for their roles in the pathogenesis of several cardiovascular disorders, including hypertension, coronary and cerebral vasospasm, atherosclerosis and diabetes, and are now considered important future therapeutic targets. A major challenge lies in further developing selective inhibitors of this pathway beyond experimental use. Consideration should perhaps also be given to widening the application of existing clinical drugs now known to also interfere with Rho-Rho-kinase signaling.
Budzyn
Klaudia
K
Department of Pharmacology, The University of Melbourne, Parkville, Victoria 3010, Australia.
Marley
Philip D
PD
Sobey
Christopher G
CG
D000818:Animals; D002317:Cardiovascular Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D009129:Muscle Tonus / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000502:physiology; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D054460:rho-Associated Kinases
D002317:Cardiovascular Agents; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D020741:rho GTP-Binding Proteins