[Rho/Rho kinase signal transduction pathway in cardiovascular disease and cardiovascular remodeling].
The small guanosine triphosphatase Rho and its target, Rho kinase, play important roles in both blood pressure regulation and vascular smooth muscle contraction. Rho is activated by agonists of receptors coupled to cell membrane G protein, such as angiotensin II and phenylephrine. Once Rho is activated, it translocates to the cell membrane where it, in turn, activates Rho kinase. Activated Rho kinase phosphorylates myosin light chain phosphatase, which is then inhibited. This sequence stimulates vascular smooth muscle contraction, stress fiber formation,and cell migration. In this way, Rho and Rho kinase activation have important effects on several cardiovascular diseases. Currently available substances that specifically inhibit this signaling pathway could offer clinical benefits in several cardiovascular, as well as noncardiovascular diseases, such as arterial hypertension, pulmonary hypertension, cerebral or coronary spasm, post-angioplasty restenosis, and erectile dysfunction.
Jalil
Jorge
J
Departamento de Enfermedades Cardiovasculares, Hospital Clínico, Pontificia Universidad Católica de Chile, Chile. jjalil@med.puc.cl
Lavandero
Sergio
S
Chiong
Mario
M
Ocaranza
María Paz
MP
D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D002465:Cell Movement; D004789:Enzyme Activation; D005260:Female; D019204:GTP-Binding Proteins; D006801:Humans; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D000960:Hypolipidemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017382:Reactive Oxygen Species; D012234:Rho Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction; D020257:Ventricular Remodeling; D054460:rho-Associated Kinases
D000960:Hypolipidemic Agents; D047908:Intracellular Signaling Peptides and Proteins; D017382:Reactive Oxygen Species; D012234:Rho Factor; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D019204:GTP-Binding Proteins