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Increased mitochondrial uncoupling proteins, respiratory uncoupling and decreased efficiency in the chronically infarcted rat heart.

Abstract：

:Heart failure patients have abnormal cardiac high energy phosphate metabolism, the explanation for which is unknown. Patients with heart failure also have elevated plasma free fatty acid (FFA) concentrations. Elevated FFA levels are associated with increased cardiac mitochondrial uncoupling proteins (UCPs), which, in turn, are associated with decreased mitochondrial respiratory coupling and low cardiac efficiency. Here, we determined whether increased mitochondrial UCP levels contribute to decreased energetics in the failing heart by measuring UCPs and respiration in mitochondria isolated from the viable myocardium of chronically infarcted rat hearts and measuring efficiency (hydraulic work/O(2) consumption) in the isolated, working rat heart. Ten weeks after infarction, cardiac levels of UCP3 were increased by 53% in infarcted, failing hearts that had ejection fractions less than 45%. Cardiac UCP3 levels correlated positively with non-fasting plasma FFAs (r=0.81; p<0.01). Mitochondria from failing hearts were less coupled than those from control hearts, as demonstrated by the lower ADP/O ratio of 1.9+/-0.1 compared with 2.5+/-0.2 in controls (p<0.05). The decreased ADP/O ratio was reflected in an efficiency of 14+/-2% in the failing hearts when perfused with 1 mM palmitate, compared with 20+/-1% in controls (p<0.05). We conclude that failing hearts have increased UCP3 levels that are associated with high circulating FFA concentrations, mitochondrial uncoupling, and decreased cardiac efficiency. Thus, respiratory uncoupling may underlie the abnormal energetics and low efficiency in the failing heart, although whether this is maladaptive or adaptive would require direct investigation.

journal_name

J Mol Cell Cardiol

journal_title

Journal of molecular and cellular cardiology

authors

Murray AJ,Cole MA,Lygate CA,Carr CA,Stuckey DJ,Little SE,Neubauer S,Clarke K

doi

10.1016/j.yjmcc.2008.01.008

subject

Has Abstract

pub_date

2008-04-01 00:00:00

pages

694-700

issue

eissn

0022-2828

issn

1095-8584

pii

S0022-2828(08)00039-4

journal_volume

pub_type

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Increased mitochondrial uncoupling proteins, respiratory uncoupling and decreased efficiency in the chronically infarcted rat heart.