Effects of Notch signalling pathway on the relationship between vascular endothelial dysfunction and endothelial stromal transformation in atherosclerosis

Mao, Yina; Jiang, Ling

doi:10.1080/21691401.2017.1337030

Cited by 6 publications

(5 citation statements)

References 39 publications

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“…The JAG1‐related signaling was retrieved in Kyoto Encyclopedia of Genes and Genomes, and the results showed that JAG1 was in the upstream of Notch signaling on Human papillomavirus infection (map05165), Breast cancer (map05224), and Endocrine resistance (map01522) signaling. Moreover, Notch signaling was associated with atherosclerosis 23,24 . Thus, it was speculated that abnormal expression of JAG1 affected Notch signaling in patients with ACS.…”

Section: Resultsmentioning

confidence: 99%

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Overexpressed miR‐335‐5p reduces atherosclerotic vulnerable plaque formation in acute coronary syndrome

Sun

Zhang

et al. 2020

Clinical Laboratory Analysis

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Background Acute coronary syndrome (ACS) may induce cardiovascular death. The correlation of mast cells related microRNAs (miRs) with risk of ACS has been investigated. We explored regulatory mechanism of miR‐335‐5p on macrophage innate immune response, atherosclerotic vulnerable plaque formation, and revascularization in ACS in relation to Notch signaling. Methods ACS‐related gene microarray was collected from Gene Expression Omnibus database. After different agomir or antagomir, or inhibitor of Notch signaling treatment, IL‐6, IL‐1β, TNF‐α, MCP‐1, ICAM‐1, and VCAM‐1 levels were tested in ACS mice. Additionally, Notch signaling‐related genes and matrix metalloproteinases (MMPs) were measured after miR‐335‐5p interference. Finally, mouse atherosclerosis, lipid accumulation, and the collagen/vessel area ratio of plaque were determined. Results miR‐335‐5p targeted JAG1 and mediated Notch signaling in ACS. miR‐335‐5p up‐regulation and Notch signaling inhibition reduced expression of JAG1, Notch pathway‐related genes, IL‐6, IL‐1β, TNF‐α, MCP‐1, ICAM‐1, VCAM‐1, and MMPs, but promote TIMP1 and TIMP2 expression. Additionally, vulnerable plaques were decreased and collagen fiber contents were observed to increase after miR‐335‐5p overexpression and Notch signaling inhibition. Conclusions Overexpression of miR‐335‐5p inhibited innate immune response of macrophage, reduced atherosclerotic vulnerable plaque formation, and promoted revascularization in ACS mice targeting JAG1 through Notch signaling.

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Section: Resultsmentioning

confidence: 99%

“…Moreover, Notch signaling components were up‐regulated in luminal endothelial cells at atherosclerotic lesions and resulted in proinflammatory response and senescence of endothelial cells 23 . Another study also suggested that Notch signaling was activated in atherosclerotic model 24 …”

Section: Discussionmentioning

confidence: 97%

Overexpressed miR‐335‐5p reduces atherosclerotic vulnerable plaque formation in acute coronary syndrome

Sun

Zhang

et al. 2020

Clinical Laboratory Analysis

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“…reported that the Notch-signaling pathway is associated with the occurrence and progression of AS. In addition, Mao and Jiang 17 demonstrated in a recent study of 2018 that the Notch-signaling pathway is activated in the vessels of AS animal models and inhibition of the Notch-signaling pathway can significantly improve AS. Moreover, Aquila et al 18 .…”

Section: Introductionmentioning

confidence: 99%

miR-133b Downregulation Reduces Vulnerable Plaque Formation in Mice with AS through Inhibiting Macrophage Immune Responses

Zheng

Chen

Mou

et al. 2019

Molecular Therapy - Nucleic Acids

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Atherosclerosis (AS) is a chronic inflammatory disease characterized by accumulating deposition of lipids in the arterial intima. Notably, macrophages participate centrally in the pathogenesis of this deadly disease. In this study, we established AS mouse models in order to investigate the effect of microRNA-133b (miR-133b) on vulnerable plaque formation and vascular remodeling in AS and explore the potential functional mechanisms. The expression of miR-133b was altered or the Notch-signaling pathway was blocked in the AS mouse models in order to evaluate the proliferation, migration, and apoptosis of macrophages. It was observed that miR-133b was upregulated in AS, which might target MAML1 to regulate the Notch-signaling pathway. AS mice with downregulated miR-133b or inhibited Notch-signaling pathway presented with a reduced AS plaque area, a decreased positive rate of macrophages, and an increased positive rate of vascular smooth muscle cells. Moreover, Notch-signaling pathway blockade or miR-133b downregulation inhibited the macrophage viability and migration and accelerated the apoptosis. This study provides evidence that downregulated miR-133b expression may inhibit the immune responses of macrophages and attenuate the vulnerable plaque formation and vascular remodeling in AS mice through the MAML1-mediated Notch-signaling pathway, highlighting miR-133b as a novel therapeutic target for AS.

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“…The upregulation of NICD acetylation mediates the activation of the Notch1 signaling pathway [ 26 , 27 , 46 ]. The Notch signaling pathway is reported to promote the progression of EndMT in human coronary endothelial cells and the development of atherosclerosis [ 47 ]. Our study revealed that DAPA inhibits EndMT through the SIRT1-regulated the Notch signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

SIRT1 mediates the inhibitory effect of Dapagliflozin on EndMT by inhibiting the acetylation of endothelium Notch1

Wang,

Li,

Zhang

et al. 2023

Cardiovasc Diabetol

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Background Endothelial–mesenchymal transition (EndMT) plays a crucial role in promoting myocardial fibrosis and exacerbating cardiac dysfunction. Dapagliflozin (DAPA) is a sodium–glucose-linked transporter 2 (SGLT-2) inhibitor that has been shown to improve cardiac function in non-diabetic patients with heart failure (HF). However, the precise mechanisms by which DAPA exerts its beneficial effects are yet to be fully elucidated. Methods Isoproterenol (ISO) was used to generate a HF model in mice. For in vitro experiments, we used TGF-β1-stimulated human umbilical vein endothelial cells (HUVECs) and mouse aortic endothelial cells (MAECs). Results Both our in vivo and in vitro results showed that EndMT occurred with decreased SIRT1 (NAD+-dependent deacetylase) protein expression, which could be reversed by DAPA therapy. We found that the protective effect of DAPA was significantly impaired upon SIRT1 inhibition. Mechanistically, we observed that SIRT1 phosphorylation, a required modification for its ubiquitination and degradation, was reduced by DAPA treatment, which induces the nucleus translocation of SIRT1 and promotes its binding to the active intracellular domain of Notch1 (NICD). This interaction led to the deacetylation and degradation of NICD, and the subsequent inactivation of the Notch1 signaling pathway which contributes to ameliorating EndMT. Conclusions Our study revealed that DAPA can attenuate EndMT induced by ISO in non-diabetic HF mice. This beneficial effect is achieved through SIRT1-mediated deacetylation and degradation of NICD. Our findings provide greater insight into the underlying mechanisms of the therapeutic effects of DAPA in non-diabetic HF. Graphical Abstract

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Effects of Notch signalling pathway on the relationship between vascular endothelial dysfunction and endothelial stromal transformation in atherosclerosis

Cited by 6 publications

References 39 publications

Overexpressed miR‐335‐5p reduces atherosclerotic vulnerable plaque formation in acute coronary syndrome

Overexpressed miR‐335‐5p reduces atherosclerotic vulnerable plaque formation in acute coronary syndrome

miR-133b Downregulation Reduces Vulnerable Plaque Formation in Mice with AS through Inhibiting Macrophage Immune Responses

SIRT1 mediates the inhibitory effect of Dapagliflozin on EndMT by inhibiting the acetylation of endothelium Notch1

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