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

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.

How Alpha Linolenic Acid May Sustain Blood–Brain Barrier Integrity and Boost Brain Resilience against Alzheimer’s Disease

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Temozolomide Efficacy and Metabolism: The Implicit Relevance of Nanoscale Delivery Systems

“…Kudarha et al worked on this problem by modifying albumin nanoparticles with TMZ by conjugating them with hyaluronic acid (HA-TMZ-NPs). The researchers achieved a significant accumulation of TMZ due to receptor interaction and caveolae-mediated endocytosis through BBB tissues [ 80 , 81 , 82 , 83 ]. According to the available data, there is a successful experience in using TMZ as part of supermagnetic nanoparticles, which showed a high degree of drug setting and encapsulation, as well as a long release period (90% of temozolomide was released for about 21 days).…”

Metabolic Pathway of Monounsaturated Lipids Revealed by In-Depth Structural Lipidomics by Mass Spectrometry

“…Lipids, as an important class of biomolecules, perform critical functions including membrane formation, energy storage, and signal transduction [ 1 – 4 ]. In recent years, our understandings of lipid biofunctions are rapidly increasing in-depth, providing more potential associations between lipids and many diseases, such as cardiovascular disease, COVID-19, and cancer [ 5 – 14 ]. In particular, lipid metabolism reprogramming has been shown to be closely related to cancer cell proliferation, tumor formation, and invasion [ 12 , 15 , 16 ].…”