POSTINFARCTION LEFT-VENTRICULAR REMODELING INDUCES CHANGES IN CREATINE-KINASE MESSENGER-RNA AND PROTEIN SUBUNIT LEVELS IN PORCINE MYOCARDIUM

Energy metabolism is altered in post-infarction remodeled pig myocardi um. To understand the basis of this abnormality, we examined the patte rn of creatine kinase (CK) gene expression and the relative content of CK protein subunits in pig hearts with proximal left circumflex coron ary artery ligation, At 2 months after infarct, both Northern and West ern blot analyses were performed on left ventricular myocardium remote frolic the infarct zone in ligation animals (n = 8), Results were com pared with data from the left ventricular myocardium from similar size d normal (control) pigs (n = 7), Steady-state levels of mitochondrial CK mRNA decreased 46% in left ventricular remodeled (LVR) heart sample s (93.40 +/- 18.60 arbitrary units) compared with controls (172.85 +/- 37.20 arbitrary units), whereas CK-M subunit mRNA levels remained unc hanged between the control and LVR groups (319.50 +/- 35.25 and 352.50 +/- 62.18 arbitrary units, respectively), The mean control group CK-M protein subunits (2.04 +/- 0.31 arbitrary units) decreased 53% (P < 0 .05) compared with the LVR group (0.95 +/- 0.25 arbitrary units). Simi larly, the mean control group (n = 4) mitochondrial CK protein subunit s (1.12 +/- 0.04 arbitrary units) decreased 30% (P < 0.05) compared wi th the LVR group (n = 4; 0.79 +/- 0.06 arbitrary units). Mean CK-B pro tein subunits in LVR pig hearts (0.84 +/- 0.23 arbitrary units) increa sed 77% compared with control (0.48 +/- 0.05 arbitrary units), The tot al CK activity did not change significantly between control hearts at 164 +/- 11 IU/mg and LVR at 212 +/- 32 IU/mg. We suggest that these al terations of the CK system represent the bioenergetic phenotype of LVR myocardium at the molecular level, The CK system response may ultimat ely, prove inadequate in meeting the abnormal energy, requirements of remodeled heart and therefore, may contribute to the transition toward failure.