The Circadian System Is Essential for the Crosstalk of VEGF-Notch-mediated Endothelial Angiogenesis in Ischemic Stroke.
10.1007/s12264-023-01042-9
- Author:
Yuxing ZHANG
1
;
Xin ZHAO
2
;
Chun GUO
1
;
Ying ZHANG
1
;
Fukang ZENG
1
;
Qian YIN
2
;
Zhong LI
1
;
Le SHAO
2
;
Desheng ZHOU
3
;
Lijuan LIU
4
Author Information
1. Department of Neurology, The First Hospital of Hunan University of Chinese Medicine, Changsha, 410007, 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. zds1101@foxmail.com.
4. Department of Neurology, The First Hospital of Hunan University of Chinese Medicine, Changsha, 410007, China. 601264967@qq.com.
- Publication Type:Journal Article
- Keywords:
Angiogenesis;
Circadian clock;
Ischemic stroke;
Notch pathway;
VEGF
- MeSH:
Rats;
Animals;
Vascular Endothelial Growth Factor A/pharmacology*;
Brain Ischemia/metabolism*;
Ischemic Stroke;
Signal Transduction;
ARNTL Transcription Factors/pharmacology*;
Neovascularization, Physiologic/physiology*
- From:
Neuroscience Bulletin
2023;39(9):1375-1395
- CountryChina
- Language:English
-
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 circadian clock in regulating angiogenesis after cerebral infarction 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 pathway 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-Notch1 pathway.
