Blockade of the Notch Signaling Pathway Promotes M2 Macrophage Polarization to Suppress Cardiac Fibrosis Remodeling in Mice With Myocardial Infarction

Abstract

Myocardial infarction (MI) is regarded as a serious ischemic heart disease on a global level. The current study set out to explore the mechanism of the Notch signaling pathway in the regulation of fibrosis remodeling after the occurrence of MI. First, experimental mice were infected with recombination signal binding protein J (RBP-J) shRNA and empty adenovirus vector, followed by the establishment of MI mouse models and detection of cardiac function. After 4 weeks of MI, mice in the sh-RBP-J group were found to exhibit significantly improved cardiac function relative to the sh-NC group. Moreover, knockdown of RBP-J brought about decreased infarct area, promoted cardiac macrophages M2 polarization, reduced cardiac fibrosis, and further decreased transcription and protein expressions of inflammatory factors and fibrosis-related factors. Furthermore, downregulation of cylindromatosis (CYLD) using si-CYLD reversed the results that knockdown of RBP-J inhibited fibrogenesis and the release of inflammatory factors. Altogether, our findings indicated that the blockade of Notch signaling promotes M2 polarization of cardiac macrophages and improves cardiac function by inhibiting the imbalance of fibrotic remodeling after MI.

PTEN inhibitor attenuates cardiac fibrosis by regulating the M2 macrophage phenotype via the PI3K/AKT/TGF-β/Smad 2/3 signaling pathway

“…The different phenotypes of M2 macrophages have different cell surface markers and secrete different cytokines and chemokines. Previous studies have revealed an antifibrotic function by inhibiting TGF-β and increasing M2 macrophages [43,50], which is consistent with our results. Further studies should be designed to explore the different phenotypes of M2 macrophages.…”

Sinapic Acid Attenuated Cardiac Remodeling After Myocardial Infarction by Promoting Macrophage M2 Polarization Through the PPARγ Pathway

“…Immunofluorescence revealed that SA can increase CD68 + /CD206 + macrophage infiltration by 23%, which suggested that SA can promote the polarization of M2 macrophages. M2 macrophages secrete various antiinflammatory factors and many studies have shown that activation and increase of M2 macrophages can attenuate ventricular remodeling (34)(35)(36)(37). Inhibition or depletion of M2 macrophage inhibiting M2 macrophage activationresulted in deterioration of cardiac function, enlargement of infarct area and increase of inflammatory cell infiltration after MI (38,39).…”

Macrophage Rmp Ameliorates Myocardial Infarction by Modulating Macrophage Polarization in Mice

“…and Inhibits Angiogenesis after MI. Studies have shown that macrophage polarization affects infarct healing after MI [3]. Flow cytometry was performed to assess macrophage polarization.…”

“…Following infarction, cardiomyocyte death and acute inflammation are induced [2]. Inflammation plays important roles during MI [3,4]. Macrophage polarization is considered to be a major factor that drives the inflammatory process [3].…”

“…Inflammation plays important roles during MI [3,4]. Macrophage polarization is considered to be a major factor that drives the inflammatory process [3]. Macrophages are generally divided into two groups: the classically activated (M1) macrophages and the alternatively activated (M2) macrophages [5,6].…”