Propionate alleviated post-infarction cardiac dysfunction by macrophage polarization in a rat model
Ming-Min Zhou1, Di-Wen Li1, Liao Xu1
1Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China; Cardiovascular Research Institute of Wuhan University, Wuhan, China; Hubei Key Laboratory of Cardiology, Wuhan, China.
Background:
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).
Methods:
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.
Results:
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.
Conclusions:
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.
Insights
Oral propionate, a short-chain fatty acid, mitigates cardiac dysfunction after myocardial infarction (MI) by promoting reparative M2 macrophages and reducing inflammation. This nutritional intervention improves cardiac remodeling and function post-MI.
Area of Science:
- Cardiovascular Research
- Immunology
- Metabolic Syndrome
Background:
- Short-chain fatty acids (SCFAs), including propionate (C3), inhibit pro-inflammatory macrophages.
- Macrophage phenotypic transition from M1 to M2 is crucial for mitigating cardiac dysfunction post-myocardial infarction (MI).
Purpose of the Study:
- To investigate the therapeutic effect of early-stage oral propionate administration on post-MI cardiac remodeling and dysfunction.
- To elucidate the role of propionate in modulating macrophage polarization and inflammatory responses in the infarcted heart.
Main Methods:
- 160 Sprague-Dawley rats were divided into sham, sham+C3, MI, and MI+C3 groups, with C3 administered orally.
- MI was induced by coronary occlusion, and assessments included macrophage classification, inflammatory factors, fibrosis, and echocardiography.
- In vitro studies used RAW264.7 cells stimulated with LPS+IFN-γ with or without propionate for western blot and cytokine analysis.
Main Results:
- Propionate administration reduced MI-induced myocardial fibrosis and attenuated cardiac function deterioration.
- Propionate promoted M2-like macrophage polarization and decreased inflammatory cytokines in the infarcted border zone.
- These effects were partly mediated by the inhibition of JNK/P38/NFκB signaling pathways.
Conclusions:
- Early-stage oral propionate acts as a nutritional intervention to alleviate chronic cardiac remodeling and dysfunction post-MI.
- Propionate modulates macrophage polarization and pro-inflammatory cytokine levels, associated with reduced JNK/P38/NFκB phosphorylation.
- This highlights propionate's potential therapeutic role in managing cardiac outcomes after myocardial infarction.
