Endogenous ghrelin attenuates pressure overload-induced cardiac hypertrophy via a cholinergic anti-inflammatory...

Area of Science:

• Cardiology
• Endocrinology
• Molecular Biology

Background:

• Cardiac hypertrophy, often caused by hypertension, significantly increases the risk of heart failure and sudden death.
• Endogenous ghrelin is known to benefit cardiac dysfunction and remodeling through the autonomic nervous system.
• The specific role of ghrelin in attenuating cardiac hypertrophy and its underlying mechanisms remain largely unexplored.

Purpose of the Study:

• To investigate the role of endogenous ghrelin in pressure overload-induced cardiac hypertrophy.
• To elucidate the mechanism by which ghrelin influences cardiac hypertrophy, focusing on the cholinergic anti-inflammatory pathway.

Main Methods:

• Cardiac hypertrophy was induced in ghrelin knockout mice and wild-type littermates using transverse aortic constriction.
• Cardiac hypertrophy was assessed by measuring heart weight/tibial length ratios and left ventricular wall thickness.
• Parasympathetic nerve activity, plasma interleukin-1β, and interleukin-6 levels were analyzed to evaluate the cholinergic anti-inflammatory pathway.

Main Results:

• Ghrelin knockout mice exhibited significantly increased cardiac hypertrophy compared to wild-type mice.
• Ghrelin deficiency led to suppressed cholinergic anti-inflammatory pathway activity, evidenced by reduced parasympathetic activity and elevated inflammatory cytokines.
• Administration of nicotine or ghrelin attenuated cardiac hypertrophy in ghrelin knockout mice by activating this pathway.

Conclusions:

• Endogenous ghrelin plays a critical role in mitigating pressure overload-induced cardiac hypertrophy.
• Ghrelin's protective effect is mediated through the activation of the cholinergic anti-inflammatory pathway.
• Targeting the ghrelin-cholinergic pathway may offer a novel therapeutic strategy for cardiac hypertrophy.