Role of Ceramide in the Aging-Related Decrease of Cardiolipin Content in the Rat Heart

Abstract—Ceramide accumulation and a decrease of cardiolipin level in cardiomyocytes are among the key reasons of mitochondrial dysfunction and the emergence of heart failure. Ceramide has a significant effect on cardiolipin metabolism, and, therefore, the aim of the present study was to assess the role of ceramide in the aging-related decrease of cardiolipin content in the rat heart. Young (sexually mature), adult, and old (3-, 12-, 24-, 30-, and 34-month-old) Wistar male rats were used in the study. A considerable decrease in the content of cardiolipin during aging was accompanied by accumulation of phosphatidic acid, a precursor of cardiolipin. Doxorubicin administration to the rats or the perfusion of an isolated heart with a buffer solution supplemented with C16-ceramide evoked an increase in ceramide levels and a decrease in the level of cardiolipin in the heart of 3-month-old rats. The reduction of ceramide content in the hearts of 24-month-old rats by means of administration of melipramine and zoledronic acid that inhibit acidic sphingomyelinase led to an increase in cardiolipin levels. The results point at a certain contribution of sphingomyelinase-dependent ceramide accumulation to the aging-related decrease of cardiolipin content that can lead to disturbances of cardiac function. Acid sphingomyelinase and cardiolipin metabolism can be important targets in the treatment of aging-related cardiac pathology.