Right ventricular hypertrophy and apoptosis after pulmonary artery banding: regulation of PKC isozymes
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- 作者：Braun ; Martin U. ; Szalai ; Palma ; Strasser ; Ruth H. ; Borst ; Mathias M.
- 关键词：Pulmonary artery bonding ; Right ventricular hypertropy ; Protein kinase C ; Apoptosis ; Renin angiotensin system
- 刊名：Cardiovascular Research
- 出版年：2003
- 出版时间：September 1, 2003
- 年：2003
- 卷：59
- 期：3
- 页码：658-667
- 全文大小：1.00 M
文摘
Objective: Pressure overload induced by pulmonary artery banding (PAB) leads to right ventricular (RV) hypertrophy and cardiomyocyte apoptosis. The present study was performed to investigate whether protein kinase C isozymes (PKC-α, PKC-βI, PKC-βII, PKC-δ and PFC-?), calcineurin and the renin–angiotensin system (RAS) contribute to PAB-induced cardiac remodeling. Methods and results: PAB in male Wistar rats for 3 weeks results in enhanced PKC activity (as determined by ELISA assay) in the cytosol and membrane fraction of the hypertrophied RV, which was accompanied by increased expression (as determined by Western blot analysis) of cytosolic PKC-δ (+72 % ), PKC-α (+49 % ), and PKC-βI (+39 % ), but not PKC-βII and PKC-?. This differential regulation of cardiac PKC isozymes was limited to the strained ventricle and was not altered in response to chronic angiotensin-converting enzyme inhibition with ramiprilate. Furthermore, no significant changes in the expression of calcineurin α and β subunits were observed in RV pressure overload compared to controls. PAB-induced cardiac apoptosis was determined using Western blot analysis by a significantly increased expression of Bax protein and caspase-3 in the hypertrophied RV, which was diminished to almost control levels by chronic ramiprilate treatment. The myocardial expression of Bcl-2 was not significantly altered in the experimental groups. Conclusion: We have shown for the first time that PAB-induced RV hypertrophy is associated with a differential regulation of cardiac PKC isozymes independent of the RAS and further provide evidence for a pivotal role of the RAS in the development of PAB-induced cardiac apoptosis.