Journal article
Hypercholesterolemia Impairs the Myocardial Angiogenic Response in a Swine Model of Chronic Ischemia: Role of Endostatin and Oxidative Stress
The Annals of thoracic surgery, Vol.81(2), pp.634-641
02/01/2006
DOI: 10.1016/j.athoracsur.2005.07.090
PMID: 16427865
Abstract
Recent studies have shown that angiogenesis is regulated by a balance between activators and inhibitors. We investigated the effects of hypercholesterolemia on the functional angiogenic response and collateral formation induced by chronic myocardial ischemia and the expression of angiogenic mediators.
Twelve Yucatan miniswine, fed either a normal (NORM, n = 6) or high cholesterol (HCHO, n = 6) diet for 13 weeks, underwent ameroid constrictor placement around the circumflex artery. Three weeks later, myocardial perfusion was quantified using isotope-labeled microspheres. Seven weeks after ameroid placement, coronary microvascular responses and myocardial perfusion were assessed. Vascular density was evaluated by PECAM-1 (CD-31) staining, and vascular endothelial growth factor, endothelial nitric oxide synthase, endostatin, and angiostatin protein levels were determined. Myocardial protein oxidation was quantified.
Coronary microvessels from HCHO pigs showed significant endothelial dysfunction. Baseline-adjusted myocardial flow at 7 weeks was significantly reduced in the HCHO animals (−0.002 ± 0.06 versus +0.23 ± 0.09 mL/min/g, HCHO versus NORM,
p = 0.04). Endostatin expression was significantly increased in the HCHO pigs (2.2-fold,
p = 0.001 versus NORM). There was a mild reduction in myocardial vascular endothelial growth factor expression (−29% ± 14%,
p = 0.09) in HCHO animals, but no difference in expression of endothelial nitric oxide synthase and angiostatin. The HCHO animals demonstrated increased myocardial protein oxidation compared with the NORM group (+155% ± 21%,
p = 0.03 versus NORM).
Ischemia-induced angiogenesis is inhibited in hypercholesterolemic pigs with a concomitant increase in endostatin expression and oxidative stress. These findings suggest that under conditions of hypercholesterolemia, coronary collateral development may be regulated by endogenous angiogenesis inhibitors such as endostatin as well as reactive oxygen species.
Details
- Title: Subtitle
- Hypercholesterolemia Impairs the Myocardial Angiogenic Response in a Swine Model of Chronic Ischemia: Role of Endostatin and Oxidative Stress
- Creators
- Munir Boodhwani - Harvard UniversityYasunari Nakai - Harvard UniversityShigetoshi Mieno - Harvard UniversityPierre Voisine - Harvard UniversityCesario Bianchi - Harvard UniversityEugenio G. Araujo - Beth Israel Deaconess Medical CenterJun Feng - Harvard UniversityKeith Michael - Harvard UniversityJian Li - Harvard UniversityFrank W. Sellke - Beth Israel Deaconess Medical Center
- Resource Type
- Journal article
- Publication Details
- The Annals of thoracic surgery, Vol.81(2), pp.634-641
- DOI
- 10.1016/j.athoracsur.2005.07.090
- PMID
- 16427865
- NLM abbreviation
- Ann Thorac Surg
- ISSN
- 0003-4975
- eISSN
- 1552-6259
- Publisher
- Elsevier Inc
- Number of pages
- 8
- Language
- English
- Date published
- 02/01/2006
- Academic Unit
- Orthopedics and Rehabilitation
- Record Identifier
- 9985167564302771
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