Changes of creatine kinase gene expression in rat heart post-myocardial
infarction
J Mol Cell Cardiol, 30 (4):
803-10 (April 1998)Neubauer, S Frank, M Hu, K Remkes, H Laser, A Horn, M Ertl, G Lohse,
M J Research Support, Non-U.S. Gov't England Journal of molecular
and cellular cardiology J Mol Cell Cardiol. 1998 Apr;30(4):803-10..Abstract
Creatine kinase (CK) plays a crucial role in cardiac energy transduction.
During chronic cardiac stress conditions leading to hypertrophy and/or
heart failure, the profile of CK isoenzyme activities changes towards
a fetal pattern with increases of BB- and MB-CK and decreases of
MM-CK and mito-CK. Changes of myocardial CK gene expression are only
indirectly reflected by measurements of CK activities. The purpose
of this work was, therefore, to determine myocardial expression of
B-, M- and sarcomeric mito-CK genes in an animal model of heart failure
where hemodynamic alterations and CK system changes are well defined,
that is, in the rat heart post-myocardial infarction. Intact residual
left ventricular myocardium was harvested 2 months following infarction
(MI; n = 7) or sham operation (sham; n = 6) after in vivo left-ventricular
end-diastolic pressure (LVEDP) was recorded. Total CK activity was
measured spectrophotometrically, CK isoenzyme distribution with agarose
gel electrophoresis. Steady state mRNA levels coding for B-, M- and
mito-CK genes were measured with quantitative PCR and were normalized
for GAPDH expression. Total CK activity tended to be reduced in MI
(5.51 +/- 0.62 IU/mg protein) compared to sham (6.77 +/- 0.24; P
= 0.55). CK isoenzyme distribution showed an increase of fetal BB-
+ MB-CK (MI 22.0 +/- 3.1%, sham 15.1 +/- 1.0%; P < 0.05), no change
of MM-CK and a decrease of mito-CK (27.0 +/- 1.5% sham, 20.8 +/-
2.0% MI: P < 0.05). Relative B-CK mRNA levels increased (sham 0.46
+/- 0.06, MI 1.03 +/- 0.09; P < 0.05) and M-CK mRNA levels decreased
(sham 1.06 +/- 0.08. MI 0.66 +/- 0.09; P < 0.05) significantly post-MI.
The increase of B-CK mRNA (r = 0.72; P = 0.009) and the decrease
of M-CK mRNA (r = 0.76; P = 0.003) correlated significantly with
in vivo LVEDP. Mito-CK mRNA levels remained unchanged after MI (sham
0.94 +/- 0.16, MI 0.98 +/- 0.09). Intact residual left-ventricular
myocardium post-MI is characterized by increased B-CK-mRNA and reduced
M-CK-mRNA expression.