Dilated cardiomyopathy impairs mitochondrial biogenesis and promotes inflammation in an age- and sex-dependent manner

Abstract

Dilated cardiomyopathy (DCM) belongs to the myocardial diseases associated with a severe impairment of cardiac function, but the question of how sex and age affect this pathology has not been fully explored. Impaired energy homeostasis, mitochondrial dysfunction, and systemic inflammation are well-described phenomena associated with aging. In this study, we investigated if DCM affects these phenomena in a sex- and age-related manner.

We analyzed the expression of mitochondrial and antioxidant proteins and the inflammatory state in DCM heart tissue from younger and older women and men.

A significant downregulation of Sirt1 expression was detected in older DCM patients. Sex-related differences were observed in the phosphorylation of AMPK that only appeared in older males with DCM, possibly due to an alternative Sirt1 regulation mechanism. Furthermore, reduced expression of several mitochondrial proteins (TOM40, TIM23, Sirt3, and SOD2) and genes (cox1, nd4) was only detected in old DCM patients, suggesting that age has a greater effect than DCM on these alterations. Finally, an increased expression of inflammatory markers in older, failing hearts, with a stronger pro-inflammatory response in men, was observed. Together, these findings indicate that age- and sex-related increased inflammation and disturbance of mitochondrial homeostasis occurs in male individuals with DCM.