Roles of notch signaling pathway and endothelial-mesenchymal transition in vascular endothelial dysfunction and atherosclerosis
Q.-Q. Lin, J. Zhao, C.-G. Zheng, J. Chun Department of Pathology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, PR China. 13706663276@139.com
OBJECTIVE: To investigate the role of the Notch signaling pathway on the endothelial-mesenchymal transition (EndMT) during vascular endothelial dysfunction and atherosclerosis.
MATERIALS AND METHODS: Human coronary artery endothelial cells (HCAEC) were treated with the exogenous Notch homolog 1 (Notch1) factor to activate the Notch1 pathway, and cells were then observed under the microscope for morphologic changes. Changes in the expression of related proteins were detected by Western blot. In vivo experiments were performed using 18 Sprague Dawley® (SD) rats, and GSI factor was used to specifically inhibit Notch pathway activation. Rats were used and randomly divided into three groups: normal diet (ND) group, high-fat diet (HFD) group, and high-fat diet + GSI (HFD+GSI) group, 6 rats in each group. Hematoxylin and eosin (H&E) staining was used to examine the cardiac aortic morphology of the rats in each treatment group. Real-time polymerase chain reaction (RT-PCR) and Western blot were used to detect the expression of Notch1, Hes1, VE-cadherin and α-SMA in the aortic tissues of rats in each group at mRNA and protein levels, respectively.
RESULTS: After HCAECs were treated with Notch1, endothelial protein levels of VE-cadherin were significantly decreased and levels of the interstitial protein α-SMA were significantly increased. In the animal model, the rats fed with high-fat diet for two months presented obvious atherosclerosis spots in their aorta, but those fed with the same diet and treated with GSI inhibitor of Notch pathway showed significantly fewer atherosclerosis signs. Compared with ND group, mRNA and protein expression levels of Notch1, Hes1 and α-SMA were significantly increased, and the expression levels of endothelial marker VE-cadherin were significantly decreased in aortas of rats in HFD group. Compared with the rats in HFD group, the rats in HFD+GSI group showed significantly reduced expression levels of Notch1, Hes1 and α-SMA.
CONCLUSIONS: The activation of Notch signaling pathway can induce the EndMT progression and promote the development of atherosclerotic lesions.
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To cite this article
Q.-Q. Lin, J. Zhao, C.-G. Zheng, J. Chun
Roles of notch signaling pathway and endothelial-mesenchymal transition in vascular endothelial dysfunction and atherosclerosis
Eur Rev Med Pharmacol Sci
Year: 2018
Vol. 22 - N. 19
Pages: 6485-6491
DOI: 10.26355/eurrev_201810_16062