Propionate alleviated post-infarction cardiac dysfunction by macrophage polarization in a rat model.

• Oral propionate in the early stage improved chronic heart function deterioration after myocardial infarction. • Propionate treatment reduced the cardiac fibrosis in infarcted border area and non-infarcted area after myocardial infarction. • Propionate treatment induced the macrophages reduction and macrophage M2-like polarization on the 3rd day after myocardial infarction. • Propionate treatment inhibited the JNK/P38/NFκB phosphorylation and pro-inflammatory cytokines production on the 3rd day after myocardial infarction. The propionate (C3), the important components of short-chain fatty acids (SCFAs), had the effect of inhibiting pro-inflammatory macrophages. Earlier macrophages phenotypic transition from pro-inflammatory M1 to reparative M2 in early stage was a central juncture of cardiac dysfunction mitigation after myocardial infarction (MI). 160 Sprague-Dawley rats were assigned to 4 groups: sham group (n = 40), sham + C3 group (n = 40), MI group (n = 40) and MI + C3 group (n = 40). The rats in sham + C3 and MI + C3 group were treated with oral sodium propionate (200 mM), and equivalent concentration of sodium chloride was administered in sham and MI group as control. After 7 days of propionate adaptive feeding, rats were anesthetized and induced the MI by coronary occlusion. The classification of macrophages, the level of inflammatory factors and inflammatory signaling were estimated at 3rd days after thoracotomy, and the extent of myocardial fibrosis was evaluated at 7th and 28th days after operation. Echocardiography was estimated on 28th day after surgery. RAW264.7 cells, stimulated by LPS + IFN-γ with or without propionate, were harvested for western blot and supernatants were collected for cytokine analysis by ELISA. Propionate administration reduced the MI-induced myocardial fibrosis in infarcted border and attenuated cardiac function deterioration compared with MI group. In comparison with MI group, propionate promoted macrophages reduction, macrophage M2-like polarization, and inflammatory cytokines decrease in infarcted border zone following MI, which partly depends on the inhibition of JNK/P38/NFκB signaling pathways. Oral propionate in early stage, as a nutritional intervention, alleviated post‐MI chronic cardiac remodeling and cardiac dysfunction at least in part by modulating macrophages polarization and pro-inflammatory cytokine, which were associated with reduction of JNK/P38/NFκB phosphorylation. [ABSTRACT FROM AUTHOR]