PKC-beta is not necessary for cardiac hypertrophy.
Studies in human and rodent models have shown that activation of protein kinase C-beta (PKC-beta) is associated with the development of pathological hypertrophy, suggesting that ablation of the PKC-beta pathway might prevent or reverse cardiac hypertrophy. To explore this, we studied mice with targeted disruption of the PKC-beta gene (knockout, KO). There were no detectable differences in expression or distribution of other PKC isoforms between the KO and control hearts as determined by Western blot analysis. Baseline hemodynamics were measured using a closed-chest preparation and there were no differences in heart rate and arterial or left ventricular pressure. Mice were subjected to two independent hypertrophic stimuli: phenylephrine (Phe) at 20 mg x kg(-1) x day(-1) sq infusion for 3 days, and aortic banding (AoB) for 7 days. KO animals demonstrated an increase in heart weight-to-body weight ratio (Phe, 4.3 +/- 0.6 to 6.1 +/- 0.4; AoB, 4.0 +/- 0.1 to 5.8 +/- 0.7) as well as ventricular upregulation of atrial natriuretic factor mRNA analogous to those seen in control animals. These results demonstrate that PKC-beta expression is not necessary for the development of cardiac hypertrophy nor does its absence attenuate the hypertrophic response.
Roman
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BB
Section of Cardiology, Department of Medicine, University of Illinois at Chicago, Illinois 60612, USA. broman@uic.edu
Geenen
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DL
Leitges
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M
Buttrick
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PM
D000818:Animals; D001011:Aorta / Q000502:physiology; D009320:Atrial Natriuretic Factor / Q000235:genetics; D015415:Biomarkers; D001794:Blood Pressure / Q000502:physiology; D006332:Cardiomegaly / Q000378:metabolism*; D002339:Carotid Arteries / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism*; D007763:Lac Operon; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000201:enzymology*; D011493:Protein Kinase C / Q000235:genetics* / Q000378:metabolism*; D064546:Protein Kinase C beta; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D020257:Ventricular Remodeling / Q000502:physiology; D001616:beta-Galactosidase
D015415:Biomarkers; D007527:Isoenzymes; D012333:RNA, Messenger; D009320:Atrial Natriuretic Factor; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D001616:beta-Galactosidase