Modification of cardiometabolic pathways as a potentially new therapeutic approach for the ageing and the failing heart?

Recent results show that caloric restriction (CR) improves existing disturbances in cardiac function independent from anti-arteriosclerotic effects. Signalling from adipose tissue to other organs via adipokine-mediated activation of AMP-activated protein kinase (AMPK) contributes to the protection by CR. Therefore, we investigated whether age and nutritional status influence the expressional pattern in cardiac and adipose tissue.

Methods: We obtained samples from the right atrium (RA), epicardial and subcutaneous adipose tissue together with a blood sample from male young/old (54,5±4,1 years/77,1±2,9 years) and normosome/obese (BMI 24,0±1,1/BMI 33,8±4,3) patients undergoing cardiac surgery. Mitochondrial respiratory function, the expression of apoptotic and load-associated markers were measured by Real-time PCR together with the expression and plasma release of selected adipokines.

Results: Mitochondrial function is depressed in older patients with a further deterioration with advanced obesity. Furthermore, the expression of proapoptotic proteins (Bcl-xS, Bax) or load-induced markers (BNP, beta MHC) are enhanced in old and in young obese patients. Protective adipokines such as adiponectin are reduced in both adipose tissues and in plasma samples in old and in young obese patients and this results in reduced AMPK.

Conclusion: These changes in myocardial and adipose tissue gene expression support the occurrence of early alteration associated with obesity even in younger patients. Cardiometabolic pathways activated during CR may yield targets for pharmacological mimetics of selected components within the spectrum of CR actions and may thus yield a promising strategy to improve cardiac function in obese patients.