Angiotensin II: a regulator of cardiomyocyte function and survival.
Angiotensin II (Ang II) has been recognized as an important myocardial inotropic modulator, but the subtleties of the signalling pathways involved remain to be fully elucidated. The inotropic effect of Ang II reflects the net outcome of competing positive and negative signalling mechanisms. In pathophysiological states such as heart failure, characterized by chronic exposure to elevated Ang II, the balance of inotropic influences could be shifted to unmask negative inotropism linked with p38 MAPK activation. Coincident with loss of inotropic balance, Ang II-mediated morphologic remodelling of the heart and apoptosis are observed and accepted to play a crucial role in contractile dysfunction and transition to heart failure. Both Ca2+-dependent and independent pathways appear to be important, and we highlight Ang II mediated CaMKII activation as a potential key integrator of these two pathways in apoptosis induction in the failing heart. To identify new therapeutic molecular targets in heart failure, further work is required to clearly establish the signalling events involved in Ang II inotropic and apoptotic signalling and the potential link between them.
Palomeque
Julieta
J
Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Medicas, Universidad Nacional de La Plata, La Plata 1900, Argentina.
Delbridge
Leanne
L
Petroff
Martin Vila
MV
D000804:Angiotensin II / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D006333:Heart Failure / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008955:Models, Cardiovascular; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000804:Angiotensin II; D048051:p38 Mitogen-Activated Protein Kinases