CHANGES OF CREATINE-KINASE GENE-EXPRESSION IN RAT-HEART POSTMYOCARDIAL INFARCTION

Creatine kinase (CK) plays a crucial role in cardiac energy transducti on. During chronic cardiac stress conditions leading to hypertrophy an d/or heart failure, the profile of CK isoenzyme activities changes tow ards 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 i ndirectly reflected by measurements of CK activities. The purpose of t his work was, therefore, to determine myocardial expression of B-, M-a nd sarcomeric mito-CK genes in an animal model of heart failure where hemodynamic alterations and CE; 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-ventricula r end-diastolic pressure (LVEDP) was recorded, Total CK activity was m easured spectrophotometrically, CK isoenzyme distribution with agarose gel electrophoresis. Steady state mRNA levels coding for B-, M- and m ito-CK genes were measured with quantitative PCR and were normalized f or GAPDH expression. Total CK activity tended to be reduced in MI (5.5 1 +/- 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 d ecrease of mito-CK (27.0 +/- 1.5% sham, 20.8 +/- 2.0% MI; P<0.05). Rel ative 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) corr elated 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-C K-mRNA and reduced M-CK-mRNA expression. (C) 1998 Academic Press Limit ed.