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Title: Simvastatin reduces endothelial NOS: caveolin-1 ratio but not the phosphorylation status of eNOS in vivo.
Austin Authors: Arora, Rajneet;Hare, David L ;Zulli, Anthony
Affiliation: Department of Medicine, University of Melbourne, Austin Health, Australia
Issue Date: 27-Jul-2012
Publication information: Journal of Atherosclerosis and Thrombosis 2012; 19(8): 705-11
Abstract: In vivo evidence for the pleiotropic effects of simvastatin on the nitric oxide synthase system is limited.To determine if simvastatin can affect the endothelial nitric oxide synthase cascade.New Zealand white rabbits (n=15) were divided: Group 1 (control) was fed a normal rabbit diet; Group 2 (MC) received a normal rabbit diet with 1% methionine (M) plus 0.5% cholesterol (C) and 5% peanut oil (atherogenic diet); Group 3 received the same diet as the MC group plus 5 mg/kg/ day simvastatin (S) orally (MCS). After 4 weeks, the abdominal aorta was collected and analyzed.Total cholesterol (TC) and total homocysteine (tHcy) were not significantly different between MCS and MC. Endothelial function was only reduced in MC (p<0.05). Although eNOS significantly increased in MC and MCS (p<0.01), simvastatin treatment significantly reduced endothelial caveolin-1 by 35% (p=0.038), causing a 2.5-fold (p=0.026) increase in the eNOS: caveolin-1 ratio. The phosphorylation of eNOS at the threonine 495 site or serine 1177 site was not affected by diet or treatment; however, a positive correlation between the two phosphorylation sites was observed (r(2)= 0.5, p=0.01).in vivo pleiotropic effects of statin therapy include decreasing endothelial caveolin-1. Other therapies designed to affect eNOS phosphorylation in vivo might be useful in further preventing CVD.
Gov't Doc #: 22850448
ORCID: 0000-0001-9554-6556
Journal: Journal of atherosclerosis and thrombosis
PubMed URL: 22850448
Type: Journal Article
Subjects: Animals
Aorta, Abdominal.cytology.drug effects.metabolism
Caveolin 1.metabolism
Cells, Cultured
Diet, Atherogenic
Endothelium, Vascular.cytology.drug effects.enzymology
Hydroxymethylglutaryl-CoA Reductase Inhibitors.pharmacology
Immunoenzyme Techniques
Nitric Oxide Synthase Type III.metabolism
Appears in Collections:Journal articles

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