Right ventricular hypertrophy and apoptosis after pulmonary artery banding: regulation of PKC isozymes

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-alpha, PKC-betaI, PKC-betaII, PKC-delta and PFC- epsilon ), calcineurin and the r...

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Veröffentlicht in:Cardiovascular research 2003-09, Vol.59 (3), p.658-667
Hauptverfasser: BRAUN, Martin U, SZALAI, Palma, STRASSER, Ruth H, BORST, Mathias M
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SZALAI, Palma
STRASSER, Ruth H
BORST, Mathias M
description 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-alpha, PKC-betaI, PKC-betaII, PKC-delta and PFC- epsilon ), calcineurin and the renin-angiotensin system (RAS) contribute to PAB-induced cardiac remodeling. 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-delta (+72%), PKC-alpha (+49%), and PKC-betaI (+39%), but not PKC-betaII and PKC- epsilon. 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 alpha and beta 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. 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.
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The present study was performed to investigate whether protein kinase C isozymes (PKC-alpha, PKC-betaI, PKC-betaII, PKC-delta and PFC- epsilon ), calcineurin and the renin-angiotensin system (RAS) contribute to PAB-induced cardiac remodeling. 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-delta (+72%), PKC-alpha (+49%), and PKC-betaI (+39%), but not PKC-betaII and PKC- epsilon. 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 alpha and beta subunits were observed in RV pressure overload compared to controls. 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Vascular system</topic><topic>Constriction, Pathologic</topic><topic>Heart</topic><topic>Heart failure, cardiogenic pulmonary edema, cardiac enlargement</topic><topic>Hypertrophy, Right Ventricular - drug therapy</topic><topic>Hypertrophy, Right Ventricular - enzymology</topic><topic>Hypertrophy, Right Ventricular - pathology</topic><topic>Immunoblotting - methods</topic><topic>Isoenzymes - metabolism</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Myocardium - chemistry</topic><topic>Myocardium - enzymology</topic><topic>Myocardium - pathology</topic><topic>Protein Kinase C - metabolism</topic><topic>Proto-Oncogene Proteins - analysis</topic><topic>Proto-Oncogene Proteins c-bcl-2 - analysis</topic><topic>Pulmonary Artery</topic><topic>Ramipril - analogs &amp; derivatives</topic><topic>Ramipril - pharmacology</topic><topic>Rats</topic><topic>Rats, Wistar</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>BRAUN, Martin U</creatorcontrib><creatorcontrib>SZALAI, Palma</creatorcontrib><creatorcontrib>STRASSER, Ruth H</creatorcontrib><creatorcontrib>BORST, Mathias M</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Cardiovascular research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>BRAUN, Martin U</au><au>SZALAI, Palma</au><au>STRASSER, Ruth H</au><au>BORST, Mathias M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Right ventricular hypertrophy and apoptosis after pulmonary artery banding: regulation of PKC isozymes</atitle><jtitle>Cardiovascular research</jtitle><addtitle>Cardiovasc Res</addtitle><date>2003-09-01</date><risdate>2003</risdate><volume>59</volume><issue>3</issue><spage>658</spage><epage>667</epage><pages>658-667</pages><issn>0008-6363</issn><eissn>1755-3245</eissn><coden>CVREAU</coden><abstract>Pressure overload induced by pulmonary artery banding (PAB) leads to right ventricular (RV) hypertrophy and cardiomyocyte apoptosis. 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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. 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.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>14499867</pmid><doi>10.1016/s0008-6363(03)00470-x</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record>
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source Oxford University Press Journals All Titles (1996-Current); MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection
subjects Angiotensin-Converting Enzyme Inhibitors - pharmacology
Animals
Apoptosis
bcl-2-Associated X Protein
Biological and medical sciences
Calcineurin - analysis
Cardiology. Vascular system
Constriction, Pathologic
Heart
Heart failure, cardiogenic pulmonary edema, cardiac enlargement
Hypertrophy, Right Ventricular - drug therapy
Hypertrophy, Right Ventricular - enzymology
Hypertrophy, Right Ventricular - pathology
Immunoblotting - methods
Isoenzymes - metabolism
Male
Medical sciences
Myocardium - chemistry
Myocardium - enzymology
Myocardium - pathology
Protein Kinase C - metabolism
Proto-Oncogene Proteins - analysis
Proto-Oncogene Proteins c-bcl-2 - analysis
Pulmonary Artery
Ramipril - analogs & derivatives
Ramipril - pharmacology
Rats
Rats, Wistar
title Right ventricular hypertrophy and apoptosis after pulmonary artery banding: regulation of PKC isozymes
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