Increased Cardiomyocyte Apoptosis and Changes in Proapoptotic and Antiapoptotic Genes bax and bcl -2 During Left Ventricular Adaptations to Chronic Pressure Overload in the Rat

• DOI: 10.1161/01.cir.99.23.3071
• Publication Date: 2012-06-12T00:42:29Z
• Authors: Gianluigi Condorelli; Carmine Morisco; Giorgio Stassi; Antonella Notte; Felicia Farina; Giuseppe Sgaramella; Assunta de Rienzo; Roberta Roncarati; Bruno Trimarco; Giuseppe Lembo
• Keywords: Pressure overload; DNA laddering

Background —Left ventricular hypertrophy (LVH) represents both an adaptive response to increased cardiac work load and a precursor state of heart failure. Recent evidence linked myocyte death by apoptosis with LVH It remained unclear, however, whether participated in the transition from left dysfunction (LVD). Methods Results —Cardiac apoptotic events changes apoptosis-specific genes were studied rat model chronic pressure overload induced transverse aortic constriction. The geometry function assessed echocardiography. Transverse constriction rats progressively developed “concentric” subsequently, LVD. A similar distribution LVD was found 18 weeks after surgery. At this time point, we determined occurrence DNA laddering, situ TUNEL labeling, light electron microscopy. monitoring proapoptotic antiapoptotic Western blot immunohistochemistry. Our data demonstrated that cardiomyocyte virtually undetectable (in sham-operated controls, SH) 0.8/10 3 1.5/10 positive nuclei LVD, respectively. Fibrosis also subendocardial midwall regions compared SH. Expression gene bax increased, whereas bcl -2 decreased Conclusions —These suggest overload, cardiomyocyte-specific contributed accompanied dramatic upregulation reduced -2/ ratio, predisposing cardiomyocytes apoptosis.