trans -2-Enoyl-CoA Reductase Tecr-Driven Lipid Metabolism in Endothelial Cells Protects against Transcytosis to Maintain Blood-Brain Barrier Homeostasis

Author:

Wang Jinxuan1,Xu Jianxiong1,Zang Guangchao2,Zhang Tao3,Wu Qi1,Zhang Hongping1,Chen Yidan1,Wang Yi4,Qin Weixi1,Zhao Shuang1,Qin Erdai1,Qiu Juhui1,Zhang Xiaojuan1,Wen Lin1,Wang Yeqi1,Wang Guixue1ORCID

Affiliation:

1. Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing 400030, China

2. Institute of Life Science, Laboratory of Tissue and Cell Biology, Lab Teaching & Management Center, Chongqing Medical University, Chongqing 400016, China

3. Chongqing Key Laboratory of Nano/Micro Composite Material and Device, School of Metallurgy and Materials Engineering, Chongqing University of Science and Technology, Chongqing 401331, China

4. College of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China

Abstract

The transport and metabolism of lipids in cerebrovascular endothelial cells (ECs) have been hypothesized to regulate blood-brain barrier (BBB) maturation and homeostasis. Long-chain polyunsaturated fatty acids (LCPUFAs) as the important lipids components of cell membranes are essential for the development and function of BBB, but the direct links of lipid metabolism and ECs barrier function remain to be established. Here, we comprehensively characterize the transcriptomic phenotype of developmental cerebrovascular ECs in single-cell resolution and firstly find that trans -2-enoyl-CoA reductase (Tecr), a very-long-chain fatty acid synthesis, is highly expressed during barriergenesis and decreased after BBB maturation. EC-specific knockout of Tecr compromises angiogenesis due to delayed vascular sprouting. Importantly, EC-specific deletion of Tecr loss restrictive quality of vascular permeability from neonatal stages to adulthood, with high levels of transcytosis, but maintains the vascular tight junctions. Moreover, lipidomic analysis shows that the expression of Tecr in ECs is associated with the containing of omega-3 fatty acids, which directly suppresses caveolae vesicles formation. These results reveal a protective role for Tecr in BBB integrity and suggest that Tecr as a novel therapeutic target in the central nervous system (CNS) diseases associated with BBB dysfunction.

Funder

Chongqing Municipal Education Commission, China

Chongqing Science and Technology Bureau

National Natural Science Foundation of China

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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