Cardiac function is not significantly diminished in hearts isolated from young caveolin-1 knockout mice.
Am J Physiol Heart Circ Physiol
; 299(4): H1183-9, 2010 Oct.
Article
en En
| MEDLINE
| ID: mdl-20693397
ABSTRACT
Matrix metalloproteinases (MMPs) are known to degrade components of the extracellular matrix. More recently, in myocardial oxidative stress injury including ischemia-reperfusion, MMP-2 is activated and degrades troponin I and α-actinin. MMP activity is regulated at several levels. We recently showed that MMP-2 is localized in the caveolae of cardiomyocytes and is negatively regulated by caveolin-1 (Cav-1). The caveolin scaffolding domain of Cav-1 inhibits MMP-2 proteolytic activity in vitro, and Cav-1(-/-) mouse hearts have increased MMP-2 activity compared with controls. Whether this increase in MMP-2 activity translates to impaired cardiac function is unknown. Hearts isolated from Cav-1(-/-) mice and their wild-type controls were perfused as isolated working hearts and physiologically challenged with increasing increments of left atrial preload (7-22.5 mmHg). The hearts were then pharmacologically challenged with increasing concentrations of isoproterenol (0.1-100 nM). Functionally, the Cav-1(-/-) hearts were similar to the controls in heart rate, peak systolic pressure, developed pressure, and rate pressure product. At higher preload pressures, the Cav-1(-/-) hearts outperformed the control hearts. Coronary flow was significantly higher in Cav-1(-/-) hearts under all conditions. The highest concentration of isoproternol increased the heart rate of Cav-1(-/-) hearts more than in controls. Western blot analysis revealed no significant changes in troponin I or α-actinin between Cav-1(-/-) hearts and their controls. There was a significant loss of MMP-2 from both knockout and control hearts during the perfusion. In summary, despite the loss of Cav-1, Cav-1(-/-) hearts show similar or better cardiac function compared with wild-type hearts following physiological challenge or ß-adrenergic stimulation in vitro, and this appears unrelated to changes in MMP-2.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Gasto Cardíaco
/
Caveolina 1
/
Corazón
/
Frecuencia Cardíaca
Límite:
Animals
Idioma:
En
Revista:
Am J Physiol Heart Circ Physiol
Asunto de la revista:
CARDIOLOGIA
/
FISIOLOGIA
Año:
2010
Tipo del documento:
Article
País de afiliación:
Canadá