Butyrate improves cardiac function and sympathetic neural remodeling following myocardial infarction in rats

Abstract

Increased inflammation is found in cardiac sympathetic neural remodeling with malignant ventricular arrhythmia (VA) following myocardial infarction (MI). Butyrate, as a microbiota-derived short-chain fatty acid, can inhibit inflammation and myocardial hypertrophy. However, the role of butyrate in sympathetic neural remodeling after MI is unknown. This study aimed to investigate whether butyrate could improve cardiac dysfunction and VA following MI by regulating inflammation and sympathetic neural remodeling. MI rats were randomized to administrate the butyrate or vehicle through intraperitoneal injection to undergo the study. Our data demonstrated that butyrate treatment preserved the partial cardiac function at 7 days post-MI. Butyrate downregulated the expression of essential for inflammatory response in the infarct border zone at 3 days post-MI. Particularly, butyrate promoted expression of M2 macrophage markers. Increased expressions of nerve growth factor and norephinephrine at 7 days after MI were inhibited in butyrate-treated rats. Furthermore, butyrate significantly decreased the density of nerve fibers for growth-associated protein-43 and tyrosine hydroxylase and resulted in fewer episodes of inducible VA. In conclusion, butyrate administration ameliorated cardiac function and VA after MI possibly through promoting M2 macrophage polarization to suppress inflammatory responses and inhibit sympathetic neural remodeling and may present an effective pharmacological strategy for the prevention of MI-related remodeling.