Role of glypican-1 in endothelial NOS activation under various steady shear stress magnitudes.
Blood flow patterns in proatherogenic and antiatherogenic regions are rather different. We hypothesize that the laminar flow with steady shear stress increased nitric oxide (NO) bioavailability while disturbed flow with low shear stress reduced it, which is mediating by glypican-1. Thus, we detected the expression of glypican-1 under different shear stress magnitudes, and tested whether the magnitude of shear stress determines the level of endothelial NO synthase (eNOS) via glypican-1 by using phosphatidylinositol phospholipase C (PI-PLC). Results revealed that the expression of glypican-1 depends on the magnitude and duration of shear stress loading. Activation of eNOS in HUVECs is downregulated by 4dyn/cm2of shear stress, but is upregulated by 15dyn/cm2. Removal of glypican-1 significantly suppressed the 15dyn/cm2shear stress-induced eNOS activity, and further reduced the 4dyn/cm2-inhibited eNOS activity. Therefore, eNOS activation depends on shear stress magnitudes and is mediated by glypican-1. The role of glypican-1 in mediating the eNOS activation under shear stress might involve in protecting the endothelial function against disturbed flow and enhancing the sensitive of the endothelial cell to laminar flow, supporting a potential role of glypican-1 against atherosclerosis.
Institute of Biomedical Engineering, School of Preclinical and Forensic Medicine, Sichuan University, Chengdu 610041, China. Electronic address: yeQgzeng@gmail.com.
Ye
Y
Zeng
Department of Physical Education, Southwest Jiaotong University, Chengdu 610031, China.
Jingxia
J
Liu
D015536:Down-Regulation / Q000235:genetics; D004789:Enzyme Activation; D053673:Glypicans / Q000235:genetics / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008954:Models, Biological; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D054801:Phosphoinositide Phospholipase C / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013314:Stress, Mechanical; D015854:Up-Regulation / Q000235:genetics
D053673:Glypicans; D012333:RNA, Messenger; D052250:Nitric Oxide Synthase Type III; D054801:Phosphoinositide Phospholipase C
Endothelial NOS; Glypican-1; HUVEC; PI-PLC; Shear stress