Changes of Creatine Kinase Gene Expression in Rat Heart Post-Myocardial Infarction

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) afterin vivoleft-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 within vivoLVEDP. 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.