Autonomic Nervous System Regulation of Epicardial Adipose Tissue: Potential Roles for Regulator of G Protein Signaling-4

Abstract

The epicardial adipose tissue (EAT) or epicardial fat is a visceral fat depot in the heart that contains intrinsic adrenergic and cholinergic nerves, through which it interacts with the cardiac sympathetic (adrenergic) and parasympathetic (cholinergic) nervous systems. These EAT nerves represent a significant source of several adipokines and other bioactive molecules, including norepinephrine, epinephrine, and free fatty acids. The production of these molecules is biologically relevant for the heart, since abnormalities in EAT secretion are implicated in the development of pathological conditions, including coronary atherosclerosis, atrial fibrillation, and heart failure. Sympathetic hyperactivity and parasympathetic (cholinergic) derangement are associated with EAT dysfunction, leading to a variety of adverse cardiac conditions, such as heart failure, diastolic dysfunction, atrial fibrillation, etc.; therefore, several studies have focused on exploring the autonomic regulation of EAT as it pertains to heart disease pathogenesis and progression. In addition, Regulator of G protein Signaling (RGS)-4 is a protein with significant regulatory roles in both adrenergic and muscarinic receptor signaling in the heart. In this review, we provide an overview of the autonomic regulation of EAT, with a specific focus on cardiac RGS4 and the potential roles this protein plays in this regulation.

Experimental study on the effect of chlorhexidine gluconate (CG)-induced atrial fibrillation on renal water and sodium metabolism

“…And G protein Signaling (RGS)-4 (RGS4) was found that may protect not only against calcium signaling-induced tachyarrhythmias and AF, but also against cholinergic-induced bradycardia. It was also reported to be potentially elevated in AF in the atrial myocytes of their AF mice recently 39 . In addition, osteopontin (OPN) is a ubiquitous pro-inflammatory cytokine, which is also known to mediate cardiac TGF-β pro-fibrotic and pro-inflammatory signaling that underlies AF 40 .…”

Significance of Endothelial Dysfunction Amelioration for Sodium–Glucose Cotransporter 2 Inhibitor-Induced Improvements in Heart Failure and Chronic Kidney Disease in Diabetic Patients

“…The epicardial adipose tissue (EAT) contains intrinsic adrenergic and cholinergic nerves, through which it interacts with the cardiac sympathetic and parasympathetic nervous systems [ 82 ]. These EAT nerves represent a significant source of bioactive molecules, including norepinephrine, epinephrine, and FA.…”

“…The abnormal secretion of unfavorable bioactive molecules from EAT is implicated in the development of coronary atherosclerosis and HF. Sympathetic hyperactivity and parasympathetic derangement are associated with EAT dysfunction, thus inducing adverse cardiac conditions, such as HF and diastolic dysfunction [ 82 ]. SGLT2is reduced BP, significantly reduced norepinephrine, and improved endothelial function [ 83 ], suggesting the beneficial effect of SGLT2i-mediated improvements in the activation of the sympathetic nervous system (SNS) on endothelial function.…”