Document Detail


Simvastatin prevents coronary microvascular remodeling in renovascular hypertensive pigs.
MedLine Citation:
PMID:  17344424     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Patients with hypertension and chronic kidney disease are at risk for cardiovascular diseases, possibly related to inflammation. Statins have beneficial anti-inflammatory effects on vascular structure regardless of cholesterol reduction. It was hypothesized that alterations in myocardial microvascular structure in swine renovascular hypertension (RVH) would be improved by simvastatin treatment. Three groups of pigs were studied after 12 wk: normal (n = 7), RVH (n = 7), or RVH+simvastatin (RVH+S; 80 mg/d; n = 6). Left ventricular muscle mass and myocardial perfusion were determined in vivo using electron beam computed tomography, and myocardial samples then were scanned ex vivo using micro-computed tomography for measurement of the spatial density of myocardial microvessels (80 to 500 microm) in situ. Capillary density and myocardial expression of inflammatory and growth factors were determined in myocardial tissue. The effects of simvastatin on inflammation-induced tube formation were evaluated in vitro in human umbilical vein endothelial cells that were exposed to TNF-alpha. RVH and RVH+S had similarly increased arterial pressure and serum creatinine. However, left ventricular hypertrophy was prevented by simvastatin, and myocardial perfusion was increased. Compared with normal, RVH showed increased spatial density of microvessels (169.6 +/- 21 versus 107.7 +/- 15.2 vessels/cm(2); P < 0.05), which was decreased in RVH+S (72.5 +/- 14.9 vessels/cm(2)), whereas capillary density remained similar to normal. RVH also increased myocardial expression of inflammatory and growth factors, which were reversed by simvastatin. Furthermore, simvastatin attenuated TNF-alpha-induced angiogenesis in vitro. Simvastatin prevents myocardial microvascular remodeling and hypertrophy in experimental RVH independent of lipid lowering. This protective effect is partly mediated by blunted expression as well as angiogenic activity of inflammatory cytokines.
Authors:
Xiang-Yang Zhu; Elena Daghini; Alejandro R Chade; Claudio Napoli; Erik L Ritman; Amir Lerman; Lilach O Lerman
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2007-03-07
Journal Detail:
Title:  Journal of the American Society of Nephrology : JASN     Volume:  18     ISSN:  1046-6673     ISO Abbreviation:  J. Am. Soc. Nephrol.     Publication Date:  2007 Apr 
Date Detail:
Created Date:  2007-03-28     Completed Date:  2007-05-31     Revised Date:  2007-12-03    
Medline Journal Info:
Nlm Unique ID:  9013836     Medline TA:  J Am Soc Nephrol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1209-17     Citation Subset:  IM    
Affiliation:
Division of Nephrology and Hypertension, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Coronary Vessels / drug effects*,  pathology
Female
Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
Hypertension, Renovascular / drug therapy*,  pathology
Microcirculation / drug effects
Neovascularization, Physiologic / drug effects
Simvastatin / therapeutic use*
Swine
Tumor Necrosis Factor-alpha / pharmacology
Grant Support
ID/Acronym/Agency:
DK73608/DK/NIDDK NIH HHS; EB000305/EB/NIBIB NIH HHS; HL65342/HL/NHLBI NIH HHS; HL77131/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 0/Tumor Necrosis Factor-alpha; 79902-63-9/Simvastatin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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