Document Detail


Atorvastatin increases myocardial indices of oxidative stress in a porcine model of hypercholesterolemia and chronic ischemia.
MedLine Citation:
PMID:  18598320     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND/AIM: Atorvastatin has previously been shown to reduce the endogenous angiogenic response to chronic ischemia in a porcine model. One possible mechanism for this effect is reduced bioavailability of nitric oxide, a key mediator of angiogenesis, secondary to increased oxygen free radicals. We sought to determine if atorvastatin modulates oxidative stress in myocardial tissue.
METHODS: Dietary induction of hypercholesterolemia was performed over 20 weeks in Yucatan swine with treated animals receiving atorvastatin 3 mg/kg/day. Chronic myocardial ischemia was induced via surgical placement of an ameroid constrictor ring around the proximal circumflex artery at age 20 weeks, followed by tissue harvest at age 27 weeks. Myocardial levels of protein, lipid, and DNA biomarkers of oxidative stress, serum levels of 8-isoprostane, nitric oxide (NO) dependent, and independent coronary microvascular reactivity, as well as isotope-labeled microsphere myocardial perfusion analysis and histologic analysis for endothelial cell density was performed.
RESULTS: Atorvastatin treatment was associated with elevated levels of myocardial protein oxidation and lipid peroxidation. Conversely, serum oxidant stress biomarkers were not elevated. Atorvastatin treatment improved nitric oxide dependent and independent microvascular reactivity, and was associated with decreased perfusion in the ischemic myocardial territory.
CONCLUSION: Treatment with atorvastatin was associated with increased levels of myocardial tissue protein and lipid oxidative stress biomarkers and a reduced functional endogenous angiogenic response, but improved coronary microvascular reactivity. Increased oxidative stress in tissues may play a role in the reduced angiogenic response seen with atorvastatin treatment in other studies.
Authors:
Neel R Sodha; Munir Boodhwani; Basel Ramlawi; Richard T Clements; Shigetoshi Mieno; Jun Feng; Shu-Hua Xu; Cesario Bianchi; Frank W Sellke
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of cardiac surgery     Volume:  23     ISSN:  0886-0440     ISO Abbreviation:  J Card Surg     Publication Date:    2008 Jul-Aug
Date Detail:
Created Date:  2008-07-07     Completed Date:  2008-10-16     Revised Date:  2014-09-18    
Medline Journal Info:
Nlm Unique ID:  8908809     Medline TA:  J Card Surg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  312-20     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adenosine Diphosphate / pharmacology
Animals
Anticholesteremic Agents / therapeutic use*
Cholesterol / blood
Coronary Circulation
Coronary Vessels / pathology,  physiopathology
DNA / metabolism
Dinoprost / analogs & derivatives,  blood,  pharmacology
Endothelium, Vascular / pathology
Female
Heptanoic Acids / therapeutic use*
Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
Hypercholesterolemia / complications,  drug therapy*,  metabolism
Lipid Peroxidation
Male
Myocardial Ischemia / complications*,  pathology,  physiopathology
Myocardium / metabolism*
Oxidation-Reduction
Oxidative Stress / drug effects*
Proteins / metabolism
Pyrroles / therapeutic use*
Swine
Swine, Miniature
Vasodilation / drug effects
Grant Support
ID/Acronym/Agency:
HL46716/HL/NHLBI NIH HHS; HL69024-02/HL/NHLBI NIH HHS; R01 HL046716/HL/NHLBI NIH HHS; R01 HL046716-17/HL/NHLBI NIH HHS; R01 HL069024/HL/NHLBI NIH HHS; T32HL076130-02/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Anticholesteremic Agents; 0/Heptanoic Acids; 0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 0/Proteins; 0/Pyrroles; 27415-26-5/8-epi-prostaglandin F2alpha; 61D2G4IYVH/Adenosine Diphosphate; 9007-49-2/DNA; 97C5T2UQ7J/Cholesterol; A0JWA85V8F/atorvastatin; B7IN85G1HY/Dinoprost
Comments/Corrections

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