Laminar shear stress generated by blood flow stimulates endothelial cells and activates signal transduction, which plays an important role in vascular homeostasis. Several lines of evidence indicate that membrane and intracellular lipids are involved in the signal transduction of biomechanical stresses. In this study, we performed global profiling of cellular lipids from human pulmonary artery endothelial cells (HPAEC) exposed to laminar shear stress. A total of 761 species of lipids were successfully annotated, with 198 of these species significantly changed in response to shear stress for 24 hours. Ether-linked lipids containing an alkyl moiety with a medium chain length (C11–C14) were uniquely upregulated, and the administration of their biosynthetic precursor 1-O-dodecyl-rac-glycerol attenuated phorbol 12-myristate 13-acetate (PMA) induced vascular cell adhesion molecule-1 (VCAM-1) expression. Given the pro-inflammatory and atherogenic roles of VCAM-1, our findings suggest that the induction of a specific group of lipids (ie, ether-linked lipids with medium length alkyl side chain) may confer atheroprotective and anti-inflammatory roles to vascular endothelial cells under flow conditions.
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