Mevastatin increases eNO synthase expression and inhibits lipid peroxidation in human endothelial cells.
Statins can protect endothelial activation independent from their lipid-lowering effects. To gain more insight in mechanisms via which HMG-CoA inhibition may attenuate endothelial activation, we assessed the effects of mevastatin on eNOS expression of non- and modified-LDL treated endothelial cells and on basal and hydrogen peroxide-induced lipid peroxidation. Oxidized-LDL (Ox-LDL), but not glycated or acylated LDL decreased eNOS expression in human endothelial cells. The extent to which Ox-LDL decreases eNOS expression depends on the extent of modification of Ox-LDL. Mevastatin increased eNOS-expression, both in the presence and absence of Ox-LDL. In addition, mevastatin decreased the H(2)O(2)-induced (100 microM) lipid peroxidation in endothelial cells. This study shows that mevastatin has protective effects on endothelial cells by inducing eNOS and by inhibiting lipid peroxidation.
Schalkwijk
Casper G
CG
Department of Clinical Chemistry, Institute for Cardiovascular Research, Vrije Univeristeit Medical Center, Amsterdam, The Netherlands. C.Schalkwijk@intmed.unimass.nl
van Dam
Bastiaan
B
Stehouwer
Coen D A
CD
van Hinsbergh
Victor W M
VW
D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects*; D008077:Lipoproteins, LDL / Q000494:pharmacology; D008148:Lovastatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D052250:Nitric Oxide Synthase Type III / Q000187:drug effects* / Q000235:genetics; D018384:Oxidative Stress; D014471:Umbilical Veins / Q000166:cytology
D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; C012258:mevastatin; D008148:Lovastatin; D006861:Hydrogen Peroxide; D052250:Nitric Oxide Synthase Type III