High-Dose Atorvastatin Improves Hypercholesterolemic Coronary Endothelial Dysfunction Without Improving the Angiogenic Response

Autor: Jian Li, Frank W. Sellke, Munir Boodhwani, Roger J. Laham, Yasunari Nakai, Cesario Bianchi, Pierre Voisine, Jun Feng, Shigetoshi Mieno, Basel Ramlawi
Rok vydání: 2006
Předmět:
Male
Vascular Endothelial Growth Factor A
Swine
Angiogenesis
Atorvastatin
Drug Evaluation
Preclinical

Myocardial Ischemia
Apoptosis
chemistry.chemical_compound
Phosphorylation
Endothelial dysfunction
biology
Caspase 3
Apoptosis Inducing Factor
Coronary Vessels
Receptor
TIE-2

Endostatins
Adenosine Diphosphate
Vasodilation
Vascular endothelial growth factor
Arterioles
Cholesterol
medicine.anatomical_structure
Matrix Metalloproteinase 9
Proto-Oncogene Proteins c-bcl-2
Caspases
HMG-CoA reductase
Swine
Miniature

Female
Fibroblast Growth Factor 2
lipids (amino acids
peptides
and proteins)

Endostatin
Cardiology and Cardiovascular Medicine
Perfusion
medicine.drug
Nitroprusside
medicine.medical_specialty
Nitric Oxide Synthase Type III
Endothelium
Hypercholesterolemia
Neovascularization
Physiologic

Nitric Oxide
Coronary Circulation
Physiology (medical)
Internal medicine
medicine
Animals
Pyrroles
Angiostatins
business.industry
medicine.disease
Endocrinology
Gene Expression Regulation
chemistry
Heptanoic Acids
15-Hydroxy-11 alpha
9 alpha-(epoxymethano)prosta-5
13-dienoic Acid

biology.protein
Endothelium
Vascular

Hydroxymethylglutaryl-CoA Reductase Inhibitors
business
Protein Processing
Post-Translational

Proto-Oncogene Proteins c-akt
Zdroj: Circulation. 114
ISSN: 1524-4539
0009-7322
DOI: 10.1161/circulationaha.105.000356
Popis: Background— Although 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) can restore endothelial function in coronary disease, in vitro and murine studies have shown their effects on myocardial angiogenesis to be biphasic and dose dependent. We investigated the functional and molecular effects of high-dose atorvastatin on the endogenous angiogenic response to chronic myocardial ischemia in hypercholesterolemic swine. Methods and Results— Yucatan pigs were fed either a normal (NORM group; n=7) or high-cholesterol diet, with (CHOL-ATR group; n=7) or without (CHOL group; n=6) atorvastatin (3 mg/kg per day) for 13 weeks. Chronic ischemia was induced by ameroid constrictor placement around the circumflex artery. Seven weeks later, microvessel relaxation responses, myocardial perfusion, and myocardial protein expression were assessed. The CHOL group demonstrated impaired microvessel relaxation to adenosine diphosphate (29±3% versus 61±6%, CHOL versus NORM; P P =NS versus NORM). Collateral-dependent myocardial perfusion, adjusted for baseline, was significantly reduced in the CHOL group (−0.27±0.07 mL/min per gram versus NORM; P P P =0.001), decreased vascular endothelial growth factor expression (−68±8%; P P =0.004 versus NORM). Conclusions— Atorvastatin improves hypercholesterolemia-induced endothelial dysfunction without appreciable changes in collateral-dependent perfusion. Increased myocardial expression of endostatin, decreased expression of vascular endothelial growth factor, and chronic Akt activation associated with atorvastatin treatment may account for the diminished angiogenic response.
Databáze: OpenAIRE