Role of hydrogen sulfide in myocardial infarction via immue response of macrophages (IRM5P.645)

Abstract

Abstract Macrophages are critical players in the inflammation, and are of central importance for healing after Myocardial infarction (MI). Hydrogen sulfide (H2S) has been demonstrated to possess cardioprotection in MI. However, it is unclear whether and how macrophage modulation by H2S can affect infarct repair. Thus, the present study was to evaluate the roles and mechanisms of H2S on macrophage post-MI. The cardiac function were improved in both WT mice and CSE KO mice, pretreated with different concentrations of NaHS (Exogenous sources of H2S). Meanwhile, the cardiac tissues that treated with NaHS exerted an increased immunohistochemical staining for macrophage marker (Galectin-3). Enhanced M2 macrophage polarization was observed in the infarcted heart treatment with NaHS following MI, along with increased production of M2 signature cytokines, such as interleukin-10 and CD163. In vitro, NaHS accelerated the migration of macrophage cell line RAW264.7. While, the inhibitors (refer to Pyk2, FAK, Src, and Rac1), not only significantly restored the migratory ability in response to the NaHS, but also blocked the activation of phospho-Src, -Pyk2, -FAK397, and -FAK925. Furthermore, the internalization of integrin β1 on the macrophage surface was induced by NaHS. Whereas, integrin β1 silencing inhibited the macrophage migration and the Src signaling activation. The results suggest that H2S may have the potential as an anti-infarct of MI by immune response of macrophages.