D. Schultz et al., SELECTIVE INDUCTION OF THE CREATINE KINASE-B GENE IN CHRONIC VOLUME OVERLOAD HYPERTROPHY IS NOT AFFECTED BY ACE-INHIBITOR THERAPY, Journal of Molecular and Cellular Cardiology, 29(10), 1997, pp. 2665-2673
Hypertrophied and failing myocardium has been shown to undergo creatin
e kinase. (CK) isoform switching, resulting in increased MB and BB com
ponents, We tested the hypothesis that chronic volume overload hypertr
ophy due to mitral regurgitation in the dog causes CK isoenzyme switch
ing and that this could be reversed by angiotensin converting enzyme i
nhibitor therapy. Thirteen adult mongrel dogs had mitral regurgitation
induced by mitral valvular chordal rupture: six were treated with ram
ipril for 4 months and seven were untreated for 4 months. Twelve dogs
were sham-operated: six received ramipril for 3 months and six were un
treated. 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; respe
ctively (P<0.05). Steady state CK-B mRNA increased three fold in treat
ed 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 rami
pril therapy does not affect this isoform switch. This may reflect a r
esponse to increased diastolic stress and more efficient energy utiliz
ation in the volume overloaded myocardium. (C) 1997 Academic Press Lim
ited.