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) 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.
Neubauer
S
S
Department of Medicine, Universität Würzburg, Germany.
Frank
M
M
Hu
K
K
Remkes
H
H
Laser
A
A
Horn
M
M
Ertl
G
G
Lohse
M J
MJ
D000818:Animals; D001794:Blood Pressure; D003402:Creatine Kinase / Q000235:genetics* / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006321:Heart / Q000503:physiopathology; D007527:Isoenzymes; D008297:Male; D009203:Myocardial Infarction / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D009206:Myocardium / Q000201:enzymology* / Q000378:metabolism; D012333:RNA, Messenger; D051381:Rats; D017208:Rats, Wistar; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology
D007527:Isoenzymes; D012333:RNA, Messenger; D003402:Creatine Kinase