Journal
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
Volume 295, Issue 5, Pages H1966-H1973Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.00727.2008
Keywords
laminar shear stress; high glucose; arachidonic acid; lipid peroxidation; glutamylcysteine ligase
Funding
- Korea Science and Engineering Foundation
- Korea government [R01-2007-000-10580-0]
- National Research Foundation of Korea [R01-2007-000-10580-0] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Mun GI, An SM, Park H, Jo H, Boo YC. Laminar shear stress inhibits lipid peroxidation induced by high glucose plus arachidonic acid in endothelial cells. Am J Physiol Heart Circ Physiol 295: H1966-H1973, 2008. First published September 12, 2008; doi:10.1152/ajpheart.00727.2008. - Elevated blood glucose and free fatty acids induce oxidative stress associated with the incidence of cardiovascular disease. In contrast, laminar shear stress (LSS) plays a critical role in maintaining vascular health. The present study examined the mechanism for the antioxidant effect of LSS attenuating the oxidative stress induced by high glucose (HG) and arachidonic acid (AA) in human umbilical vein endothelial cells. HG and AA synergistically decreased cell viability and increased glutathione (GSH) oxidation and lipid peroxidation. The lipid peroxidation was markedly prevented by LSS as well as tetrahydrobiopterin (BH4) and GSH. LSS increased BH4 and GSH contents, and expression of GTP cyclohydrolase-1 and glutamylcysteine ligase (GCL) involved in their biosynthesis. Inhibition of GCL activity by DL-buthionine-(S, R)- sulfoximine and small-interfering RNA-mediated knockdown of GCL lessened the antioxidant effect of LSS. Therefore, it is suggested that LSS enhances antioxidant capacity of endothelial cells and thereby attenuates the oxidative stress caused by cardiovascular risk factors.
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