Research Article
Loss of cardiac tetralinoleoyl cardiolipin in human and experimental heart failure

https://doi.org/10.1194/jlr.M600551-JLR200Get rights and content
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The mitochondrial phospholipid cardiolipin is required for optimal mitochondrial respiration. In this study, cardiolipin molecular species and cytochrome oxidase (COx) activity were studied in interfibrillar (IF) and subsarcolemmal (SSL) cardiac mitochondria from Spontaneously Hypertensive Heart Failure (SHHF) and Sprague-Dawley (SD) rats throughout their natural life span. Fisher Brown Norway (FBN) and young aortic-constricted SHHF rats were also studied to investigate cardiolipin alterations in aging versus pathology. Additionally, cardiolipin was analyzed in human hearts explanted from patients with dilated cardiomyopathy. A loss of tetralinoleoyl cardiolipin (L4CL), the predominant species in the healthy mammalian heart, occurred during the natural or accelerated development of heart failure in SHHF rats and humans. L4CL decreases correlated with reduced COx activity (no decrease in protein levels) in SHHF cardiac mitochondria, but with no change in citrate synthase (a matrix enzyme) activity. The fraction of cardiac cardiolipin containing L4CL became much lower with age in SHHF than in SD or FBN mitochondria. In summary, a progressive loss of cardiac L4CL, possibly attributable to decreased remodeling, occurs in response to chronic cardiac overload, but not aging alone, in both IF and SSL mitochondria. This may contribute to mitochondrial respiratory dysfunction during the pathogenesis of heart failure.

phospholipids
mitochondria
linoleic acid
cytochrome oxidase
congestive heart failure
cardiomyopathy
aging

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Published, JLR Papers in Press, April 10, 2007.

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G. C. Sparagna and A. J. Chicco contributed equally to this work.