Signaling and expression for mitochondrial membrane proteins during left ventricular remodeling and contractile failure after myocardial infarction.
OBJECTIVE
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.
Ning
X H
XH
Department of Pediatrics, University of Washington, Seattle, USA.
Zhang
J
J
Liu
J
J
Ye
Y
Y
Chen
S H
SH
From
A H
AH
Bache
R J
RJ
Portman
M A
MA
D000818:Animals; D015415:Biomarkers; D015152:Blotting, Northern; D015153:Blotting, Western; D018450:Disease Progression; D015870:Gene Expression; D006333:Heart Failure / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D008929:Mitochondria, Heart / Q000378:metabolism*; D000226:Mitochondrial ADP, ATP Translocases / Q000235:genetics* / Q000378:metabolism; D009200:Myocardial Contraction; D006180:Proton-Translocating ATPases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D015398:Signal Transduction; D013552:Swine; D020257:Ventricular Remodeling
D015415:Biomarkers; D012333:RNA, Messenger; D000226:Mitochondrial ADP, ATP Translocases; D006180:Proton-Translocating ATPases