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

Yuxing Zhang ¹Xin Zhao ²Chun Guo ³Ying Zhang ⁴Fukang Zeng ¹Qian Yin ²Zhong Li ³Le Shao ⁵Desheng Zhou ³Lijuan Liu³

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作者信息

1. 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
2. Hunan University of Chinese Medicine,Changsha 410006,China
3. Department of Neurology,The First Hospital of Hunan University of Chinese Medicine,Changsha 410007,China
4. Department of Neurology,The First Hospital of Hunan University of Chinese Medicine,Changsha 410007,China;Hunan University of Chinese Medicine,Changsha 410006,China
5. 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
折叠

Abstract

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.

Key words

Circadian clock/Ischemic stroke/Angiogenesis/VEGF/Notch pathway

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基金项目

National Natural Science Foundation for Young Scholars of China(82004346)

National Natural Science Foundation for Young Scholars of China(82104766)

Natural Science Foundation of Hunan Province(2021JJ30521)

Natural Science Foundation of Hunan Province(2021JJ40424)

Open Fund for the Firstclass Discipline of Integrated Traditional Chinese and Western Medicine of Hunan University of Chines(2020ZXYJH38)

Open Fund for the Firstclass Discipline of Integrated Traditional Chinese and Western Medicine of Hunan University of Chines(2020ZXYJH39)

Natural Science Foundation of Changsha(kq2208202)

Universitylevel Fund Project of Hunan University of Chinese Medicine(2021XJJJ039)

出版年

2023

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

参考文献量79

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