Abstract
Peroxidation of membrane polyunsaturated fatty acids is a hallmark feature of myocardial injury associated with aging and heart failure. We examined the extent to which changes in myocardial membrane fatty acid composition predict markers of lipoxidative stress associated with aging and heart failure in the rat and human myocardium. In Fisher 344 rats, aging was associated with a marked desaturation of myocardial phospholipids, represented by increases in 22:6 and the 20:4/18:2 ratio that correlated closely with increases in malondialdehyde (MDA) and 4‐hydroxnonenal (HNE)‐protein adducts. These phenomena occurred at an earlier age and to a greater extent in SHHF rats genetically predisposed to hypertensive cardiomyopathy. No independent effect of aging on these parameters was observed in human hearts, but the presence of dilated cardiomyopathy significantly increased membrane 22:6 content, which closely paralleled increases in MDA. No robust or consistent relationships were found between glutathione peroxidase‐4 or superoxide dismutase (SOD) isozyme protein content and MDA or HNE, though both tended to correlate positively with MDA in rats and humans, and SODs correlated positively with 22:6 in the human heart. In conclusion, the desaturation of membrane phospholipids may represent an important contributor to lipoxidative stress in aged and/or failing myocardium. Supported by a grant from the AHA.
Published Version
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