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.
Highlights
Myocardial infarction (MI), precipitated by the blockade of a coronary artery, ranks as one of the leading causes of mortality and disability across the world [1]
It was found that left ventricular end-diastolic diameter (LVED) and left ventricular end-systolic diameter (LVES) were both significantly increased, while Left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were both markedly decreased in the MI group, which indicated that the systolic and diastolic functions of the heart were significantly impaired due to coronary artery ligation, compounding to obvious cardiac dysfunction
Based on the aforementioned evidence, the current study carried out a series of experiments to explore the potential mechanism of the Notch signaling pathway in regulating macrophage polarization in fibrosis remodeling after MI
Summary
Myocardial infarction (MI), precipitated by the blockade of a coronary artery, ranks as one of the leading causes of mortality and disability across the world [1]. Cardiac fibrosis is established as a common manifestation of cardiac remodeling after MI, whereas the phenomenon of excessive remodeling of myocardial fibers can precipitate a downhill cascade, leading to chronic heart failure and death [3]. The M1 form of macrophages is known to promote the progression of inflammatory responses, whereas M2 macrophages exert a certain anti-inflammatory effect and a promoting effect on the proliferation of endothelial cells and fibroblasts, collectively regulating the immune microenvironment at the site of infarction by influencing their functional characteristics [5]. There is evidence to suggest the important regulatory role of macrophage polarization in cardiac remodeling after MI in humans [6]. The underlying regulatory mechanism and potential effects of macrophage polarization concerning MI remain unknown
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
