Notch signaling promotes angiogenesis and improves cardiac function after myocardial infarction

Abstract

Currently, the role of Notch signaling during myocardial infarction (MI) remains controversy. In this study we used in vitro and in vivo approaches to investigate the role of Notch signaling in MI. Using cultured human umbilical vein endothelial cells exposed to hypoxia/reoxygenation (H/R), we demonstrated that H/R inhibited the proliferation, VEGF secretion, and tube formation of HUVECs, and these effects were correlated with the inhibition of Notch signaling. Furthermore, these effects were antagonized by overexpression of NICD but aggravated by knockdown of NICD. In addition, in MI model rats we found that heart dysfunction and angiogenesis in model rats was partly improved by NICD overexpression but was aggravated by knockdown of NICD. In conclusion, these data demonstrate that Notch signaling is downregulated in H/R injury in the hearts. Artificial activation of Notch signaling could promote myocardial survival and angiogenesis and improve cardiac function following H/R injury.

MicroRNA‐210 regulates human trophoblast cell line HTR‐8/SVneo function by attenuating Notch1 expression: Implications for the role of microRNA‐210 in pre‐eclampsia

“…Furthermore, previous studies have demonstrated that miR‐210 plays crucial roles by targeting a large number of genes (X.‐L. Zhou et al, ), including NOTCH1 (Y. L. Lou et al, ). Indeed, in the human placenta, NOTCH1 participates in the development of the EVT lineage (Sandra et al, ).…”

“…Accumulating evidence has suggested that miR-210 plays critical roles in various pathophysiological processes, such as angiogenesis, ischemia, inflammation, and tumorigenesis (Chan & Loscalzo, 2010;Herr et al, 2011). Furthermore, previous studies have demonstrated that miR-210 plays crucial roles by targeting a large number of genes (X.-L. Zhou et al, 2018), including NOTCH1 (Y. L. Lou et al, 2012). Indeed, in the human placenta, NOTCH1 participates in the development of the EVT lineage (Sandra et al, 2016).…”

Extracellular Vesicles From Notch Activated Cardiac Mesenchymal Stem Cells Promote Myocyte Proliferation and Neovasculogenesis

“…Neovasculogenesis has the potential to salvage ischemic myocardium at early stages post-MI. Notch1 signaling plays a critical role in postnatal angiogenesis including cardiac angiogenesis during ischemia (Yoshida et al, 2014;Zhou et al, 2018), thus enhancing survival of cardiac cells. Notch1 activation promotes VSMC differentiation of CDC through an RBPJdependent signaling pathway (Chen et al, 2012).…”

Notch receptor expression in Trypanosoma cruzi‐infected human umbilical vein endothelial cells treated with benznidazole or simvastatin revealed by microarray analysis

“…In embryos, the Notch signaling pathways function mainly in heart morphogenesis and coronary angiogenesis (Quillard and Charreau, 2013; Luxan et al, 2016a, b). In adults, this pathway may contribute to endothelial barrier maintenance and regulate angiogenesis (Zhou et al, 2018). However, since all its components are present, it can be activated after the appearance of specific stressors, which in the heart can be ischemia (Li et al, 2010).…”

“…It is postulated that during cardiac ischemic processes, such as acute myocardial infarction, there is a notch‐driven trend toward increasing cardiac progenitor cell differentiation. Most likely, this process will replace lost cardiomyocytes, decrease conversion from fibroblasts to myofibroblasts, and promote collateral vessels by angiogenesis, as a part of the overall effort to further reduce the scar area (Zhou et al, 2018).…”