首页|The Circadian System Is Essential for the Crosstalk of VEGF-Notch-mediated Endothelial Angiogenesis in Ischemic Stroke

The Circadian System Is Essential for the Crosstalk of VEGF-Notch-mediated Endothelial Angiogenesis in Ischemic Stroke

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Ischemic stroke is a major public health problem worldwide.Although the circadian clock is involved in the process of ischemic stroke,the exact mechanism of the cir-cadian clock in regulating angiogenesis after cerebral infarc-tion remains unclear.In the present study,we determined that environmental circadian disruption(ECD)increased the stroke severity and impaired angiogenesis in the rat middle cerebral artery occlusion model,by measuring the infarct volume,neurological tests,and angiogenesis-related protein.We further report that Bmal1 plays an irreplaceable role in angiogenesis.Overexpression of Bmal1 promoted tube-forming,migration,and wound healing,and upregulated the vascular endothelial growth factor(VEGF)and Notch path-way protein levels.This promoting effect was reversed by the Notch pathway inhibitor DAPT,according to the results of angiogenesis capacity and VEGF pathway protein level.In conclusion,our study reveals the intervention of ECD in angiogenesis in ischemic stroke and further identifies the exact mechanism by which Bmal1 regulates angiogenesis through the VEGF-Notchl pathway.

Circadian clockIschemic strokeAngiogenesisVEGFNotch pathway

Yuxing Zhang、Xin Zhao、Chun Guo、Ying Zhang、Fukang Zeng、Qian Yin、Zhong Li、Le Shao、Desheng Zhou、Lijuan Liu

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Department of Neurology,The First Hospital of Hunan University of Chinese Medicine,Changsha 410007,China

Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases,Changsha 410208,China

Hunan University of Chinese Medicine,Changsha 410006,China

Laboratory of Prevention and Transformation of Major Diseases in Internal Medicine of Traditional Chinese Medicine,Changsha 410007,China

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National Natural Science Foundation for Young Scholars of ChinaNational Natural Science Foundation for Young Scholars of ChinaNatural Science Foundation of Hunan ProvinceNatural Science Foundation of Hunan ProvinceOpen Fund for the Firstclass Discipline of Integrated Traditional Chinese and Western Medicine of Hunan University of ChinesOpen Fund for the Firstclass Discipline of Integrated Traditional Chinese and Western Medicine of Hunan University of ChinesNatural Science Foundation of ChangshaUniversitylevel Fund Project of Hunan University of Chinese Medicine

82004346821047662021JJ305212021JJ404242020ZXYJH382020ZXYJH39kq22082022021XJJJ039

2023

10.1007/s12264-023-01042-9

神经科学通报(英文版)
中国科学院上海生命科学研究院

神经科学通报(英文版)

CSTPCDCSCD
影响因子：0.741
ISSN：1673-7067
年,卷(期)：2023.39(9)
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