Selective induction of the creatine kinase-B gene in chronic volume overload hypertrophy is not affected by ACE-inhibitor therapy.
Hypertrophied and failing myocardium has been shown to undergo creatine kinase (CK) isoform switching, resulting in increased MB and BB components. We tested the hypothesis that chronic volume overload hypertrophy due to mitral regurgitation in the dog causes CK isoenzyme switching and that this could be reversed by angiotensin converting enzyme inhibitor therapy. Thirteen adult mongrel dogs had mitral regurgitation induced by mitral valvular chordal rupture: six were treated with ramipril for 4 months and seven were untreated for 4 months. Twelve dogs were sham-operated: six received ramipril for 3 months and six were untreated. Left ventricular end-diastolic volume increased from 58+/-4 to 104+/-10 ml in untreated (P<0.001) and from 55+/-3 to 91+/-6 ml in treated dogs (P<0.01) as LV mass/volume ratio decreased in both untreated (1. 60+/-0.07 to 1.13+/-0.08 g/ml, P<0.001) and treated dogs (1.44+/-0.06 to 1.20+/-0.08 g/ml, P<0.01). CK-MB isoform was 7.4+/-1.1% in normal shams and increased to 13.5+/-1.9% and 18.1+/-3.0% in both treated and untreated mitral regurgitation dogs; respectively (P<0. 05). Steady state CK-B mRNA increased three-fold in treated and untreated dogs with mitral regurgitation (P<0.003) compared to normals, while CK-M mRNA expression did not differ in all groups. Thus, chronic volume overload hypertrophy of mitral regurgitation induces CK isoform switching by selective induction of the CK-B gene, and ramipril therapy does not affect this isoform switch. This may reflect a response to increased diastolic stress and more efficient energy utilization in the volume overloaded myocardium.
Schultz
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Division of Cardiovascular Disease, Hypertension and Vascular Biology, Birmingham Veteran Affairs Medical Center, University of Alabama at Birmingham, University Station, Birmingham, Alabama 35294, USA.
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Bishop
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Billadello
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Dell'Italia
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D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D003402:Creatine Kinase / Q000235:genetics* / Q000378:metabolism; D004285:Dogs; D005786:Gene Expression Regulation / Q000187:drug effects*; D006352:Heart Ventricles / Q000166:cytology; D006439:Hemodynamics; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy / Q000378:metabolism*; D007527:Isoenzymes; D008279:Magnetic Resonance Imaging; D012333:RNA, Messenger; D017257:Ramipril / Q000627:therapeutic use*
D000806:Angiotensin-Converting Enzyme Inhibitors; D007527:Isoenzymes; D012333:RNA, Messenger; D003402:Creatine Kinase; D017257:Ramipril