- 作者：Narain Moorjani ; Pedro Catarino ; Danyah Trabzuni ; Soad Saleh ; Azad Moorji ; Nduna Dzimiri ; Futwan Al-Mohanna ; Stephen Westaby ; Manzoor Ahmad
- 关键词：Bcl-2 proteins ; Cardiomyocyte apoptosis ; Endomyocardial biopsy ; Heart failure ; Pressure overload
- 刊名：International Journal of Cardiology
- 出版年：2007
- 出版时间：2 March 2007
- 年：2007
- 卷：116
- 期：1
- 页码：27-33
- 全文大小：548 K
Cardiomyocyte apoptosis is implicated in the pathogenesis of heart failure and mitochondria play an important role in this mode of cell death. In this study, activity of the Bcl-2 family of mitochondrial apoptotic proteins and their regulator (p53) were assessed during the transition to heart failure.
Methods
Ten adult male sheep were banded with a variable aortic constriction device. This was progressively inflated to increase left ventricular (LV) afterload. The sheep were monitored echocardiographically, measuring LV Mass Index (LVMI), diastolic LV Internal Diameter (LVIDd) and Fractional Shortening (FS). Serial LV endomyocardial biopsies were obtained, to measure expression of p53 and Bcl-2 family proteins by Western blotting.
Results
Over the first 3–4 weeks, the sheep developed hypertrophy (LVMI 79.5 ± 4.6 vs. 44.0 ± 3.0 g/m2, p < 0.01), followed by gradual LV dilatation (LVIDd 4.23 ± 0.08 vs. 3.39 ± 0.07 cm, p < 0.01). Ventricular function remained stable until 7–8 weeks post banding, when there was significant deterioration (FS 18.3 ± 2.4 vs. 46.9 ± 2.6 % , p < 0.01), associated with clinical heart failure. Upregulation of the Bax/Bcl-2 ratio, associated with increased levels of p53, was demonstrated in each of the echocardiographically defined stages (LV hypertrophy, LV dilatation and LV failure). In parallel, significantly higher levels of anti-apoptotic protein (Bcl-xL) was associated with LV dilatation and failure.
Conclusions
Upregulation of Bax/Bcl-2 ratio occurs during the transition to heart failure and in particular with the initial hypertrophic response. Increase in expression of the anti-apoptotic protein Bcl-xL suggests possible concomitant compensatory mechanisms being activated during the transition to heart failure.