Key result
Post-MI heart failure links to ~60% lower myocardial ANT expression in swine models.
Why the study?
Altered signaling for mitochondrial membrane proteins during postinfarction remodeling and their relation to myocardial adaptation were not well understood.
Maintained signaling for key mitochondrial membrane proteins (ANT and betaF1) is associated with successful myocardial adaptation after infarction, whereas their reduction relates to contractile failure.
Answers are grounded in this paper and cite their sources.
Mitochondrial protein reductions may mark maladaptive post-MI remodeling; hypothesis-generating in porcine model and leaves human translation open.
OBJECTIVES: This study was conducted to test hypotheses stating that: 1) altered signaling for mitochondrial membrane proteins occurs during postinfarction remodeling, and 2) successful myocardial adaptation relates to promotion of specific mitochondrial membrane components. BACKGROUND: Abnormalities in high-energy phosphate content and limitations in adenosine 5'-triphosphate (ATP) synthesis rate occur during the transition to contractile failure from compensatory remodeling after left ventricular infarction. The adenine nucleotide translocator (ANT) and F1-ATPase respectively regulate mitochondrial adenosine 5'-diphosphate (ADP)/ATP exchange and ADP-phosphorylation, which are key components of high-energy phosphate metabolism. METHODS: Steady-state mRNA and protein expression for ANT isoform1 and the beta subunit of the F1-ATPase (betaF1) were analyzed in myocardium remote from the infarction zone eight weeks after left circumflex coronary artery ligation in pigs, demonstrating either successful left ventricular remodeling (LVR, n = 8) or congestive heart failure (CHF, n = 4) as determined by clinical and contractile performance parameters. RESULTS: Substantial reductions in steady-state mRNA expression for ANT1 and betaF1 relative to normal (n = 8) occur in CHF, p < 0.01, but not in LVR. Relative expression for both proteins coordinated with their respective steady-state mRNA levels; CHF at 40% normal, p < 0.05 for ANT and 70% normal for betaF1, p < 0.05. CONCLUSIONS: Maintained signaling for major mitochondrial membrane proteins occurs in association with successful remodeling and adaptation after infarction. Reduced expression of these proteins relates to limited ATP synthesis capacity and high energy phosphate kinetic abnormalities previously demonstrated in CHF. These findings imply that mitochondrial processes participate in myocardial remodeling after infarction.
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Zhang et al. (2000) studied Left ventricular remodeling and congestive heart failure post-infarction (n=20). Congestive heart failure post-infarction vs. Normal controls and successful left ventricular remodeling was evaluated on Steady-state mRNA and protein expression for ANT isoform1 and betaF1 in myocardium remote from the infarction zone (p=<0.01). In pigs 8 weeks post-myocardial infarction, congestive heart failure was associated with significantly reduced protein expression for ANT (40% of normal, p<0.05) and betaF1 (70% of normal, p<0.05).
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