Cardiolipin Metabolism in Experimental and Human Heart Failure
Heart failure accounts for approximately 5% of all medical admissions and is the single most common cause of hospital admissions in individuals aged 65 years and over. The biochemical mechanisms for the development of heart failure are beginning to emerge. Cardiolipin is a major mitochondrial membrane phospholipid required for the activity of key mitochondrial enzymes involved in cellular energy production. Loss of cardiolipin results in the inability of mitochondria to sustain oxidative phosphorylation. Cardiolipin metabolism is altered leading to reduction in tetralinoleoyl-cardiolipin levels in experimental animal models of heart failure and in humans. This loss in tetralinoleoyl-cardiolipin results in reduced mitochondrial function which may contribute to the development of heart failure. Thus, cardiolipin biosynthetic and remodeling enzymes may represent targets for pharmacotherapeutic modulation in both left ventricular- as well as right ventricular-mediated heart failure.
KeywordsCardiolipin Heart failure Mitochondria Phospholipid Biosynthesis Remodeling Tafazzin Huntington disease Persistent pulmonary hypertension Hypertensive heart failure–prone rat Genetic disease Yeast artificial chromosome mouse Barth syndrome
The author wishes to acknowledge the contribution of Dr. Harjot Saini-Chohan for Figs. 2 and 3, Dr. Shyamala Dakshinamurti for PPHN piglet hearts and Dr. Simonetta Sipione for YAC128 mouse hearts. This work was supported by a grant from the Heart and Stroke Foundation of Manitoba, the Barth Syndrome Foundation of Canada, and the Huntington Foundation of Canada. G.M.H. is a Canada Research Chair in Molecular Cardiolipin Metabolism.
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