Sacubitril/valsartan alleviates myocardial infarction-induced inflammation in mice by promoting M2 macrophage polarisation via regulation of PI3K/Akt pathway

Background: Macrophage polarisation-mediated inflammation plays a critical role in ventricular remodelling after myocardial infarction (MI). Sacubitril/Valsartan (Sac/Val) is an angiotensin receptor-neprilysin inhibitor that has shown beneficial effects on MI and heart failure. This study aims to further explore the mechanisms by which Sac/Val exerts its protective effects against MI.

Methods: A mouse MI model was induced by ligating the left anterior descending coronary artery, followed by Sac/Val administration. TTC staining and Masson trichrome staining were employed for estimating myocardial infarct size and fibrosis, respectively. The expression levels of proinflammatory factors were determined by ELISA and RT-qPCR. Flow cytometry and immunofluorescence staining were implemented to detect CD206-positive cell infiltration in mouse hearts. Western blotting was conducted to assess protein levels of Arg1, pro-fibrotic factors, and PI3K/Akt signalling-related markers.

Results: Sac/Val treatment reduced myocardial infarct size and fibrosis in mice after MI. Sac/Val administration decreased proinflammatory cytokine production and facilitated M2 macrophage polarisation in MI mouse cardiac tissues. Sac/Val activated PI3K/Akt signalling in MI mouse hearts. Blocking PI3K/Akt signalling counteracted Sac/Val-mediated protective effects in MI mice.

Conclusion: Sac/Val ameliorates MI-induced inflammation by facilitating M2 macrophage polarisation and activating PI3K/Akt signalling.

M2 macrophages; Myocardial infarction; PI3K/Akt; inflammation; sacubitril/valsartan.