Can elevated plasma Adiponectin and Ghrelin counteract inflammation in the aging heart?

Abstract

The adaptability of the heart helps in sustaining its function under severe pressure overload conditions, including myocardial infarction and heart failure. Immune response and inflammatory changes are among the adaptive changes the heart relies on when challenged with stress or pressure stimuli. However, the immune system homeostasis declines with advancing age and increases the susceptibility to develop heart failure. Dissecting the inflammatory changes associated with age could develop novel rejuvenating therapies for an aging population. The older mice show tremendous cardiac adaptations with advancing age. However, how the old heart adapts and survives the chronic stress that increases with age are unclear. The potential involvement of inflammatory alterations in older heart has not been recognized previously. We performed a screen of genes and proteins from RNA-seq and proteome profiles for regulators of cardiac inflammation in the old heart. We identified several pro-inflammatory and anti-inflammatory factors that belong to several immune response pathways. The inflammatory mediator plasma leptin levels increase at 3 months and decrease in the 18 months older mice. We found that the activated inflammatory gene program is associated with reduced left ventricular ejection fraction and vice-versa in the old mice. We also observed that elevated plasma levels of adiponectin and ghrelin are associated with reduced inflammatory molecules, including leptin, in these animals. We speculate that the induction of adiponectin and ghrelin secretion and downregulation of leptin secretion appears to encounter the elevated inflammatory gene program observed in the aging heart.