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Hypercholesterolemia Impairs the Myocardial Angiogenic Response in a Swine Model of Chronic Ischemia: Role of Endostatin and Oxidative Stress  Munir Boodhwani,

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Presentation on theme: "Hypercholesterolemia Impairs the Myocardial Angiogenic Response in a Swine Model of Chronic Ischemia: Role of Endostatin and Oxidative Stress  Munir Boodhwani,"— Presentation transcript:

1 Hypercholesterolemia Impairs the Myocardial Angiogenic Response in a Swine Model of Chronic Ischemia: Role of Endostatin and Oxidative Stress  Munir Boodhwani, MD, Yasunari Nakai, MD, PhD, Shigetoshi Mieno, MD, PhD, Pierre Voisine, MD, Cesario Bianchi, MD, PhD, Eugenio G. Araujo, DVM, PhD, Jun Feng, MD, PhD, Keith Michael, BS, Jian Li, MD, PhD, Frank W. Sellke, MD  The Annals of Thoracic Surgery  Volume 81, Issue 2, Pages (February 2006) DOI: /j.athoracsur Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions

2 Fig 1 Microvascular reactivity. Percent relaxation to increasing concentrations of vasodilating agents after preconstriction with U (A) Responses to endothelium-dependent vasodilator adenosine diphosphate (ADP). (B) Endothelium-independent vasodilator sodium nitroprusside (SNP). (C) Vascular endothelial growth factor (VEGF) in both the normal diet (NORM) group (circles) and the high-cholesterol diet (HCHO) group (triangles). (*p = versus NORM; **p = 0.02 versus NORM.) The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions

3 Fig 2 Myocardial perfusion. Baseline-adjusted circumflex territory myocardial blood flow in normocholesterolemic (NORM) and hypercholesterolemic (HCHO) swine after circumflex ameroid occlusion. Adjusted circumflex territory flow was significantly reduced in the CHOL group compared with the NORM group, both at rest (A) and with pacing (B). (*p = 0.04 versus NORM; **p = versus NORM.) The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions

4 Fig 3 Capillary endothelial cell density. Immunohistochemistry of myocardial sections with an anti-PECAM-1 antibody showing staining of endothelial cells in (A) normal diet (NORM) pigs versus (B) high-cholesterol diet (HCHO) pigs. Arrows point to microvessels. (C) The capillary endothelial density per high power field (0.264 mm2) was significantly lower in the circumflex territory of the HCHO group. (*p = 0.05 versus NORM.) The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions

5 Fig 4 Western blot analysis of myocardial endostatin expression. Endostatin expression was significantly increased (2.2-fold) in high-cholesterol diet (HCHO) animals compared with normal diet (NORM) animals. (*p = ) The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions

6 Fig 5 Western blot analysis of myocardial eNOS expression. The eNOS expression was similar between the high-cholesterol diet (HCHO) and normal diet (NORM) animals. (p = 0.42.) The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions

7 Fig 6 Western blot analysis of myocardial vascular endothelial growth factor (VEGF) expression. The expression of VEGF was slightly reduced in high-cholesterol diet (HCHO) animals compared with normal diet (NORM) animals. (*p = ) The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions

8 Fig 7 Immunoblot analysis of myocardial oxidized proteins. The high-cholesterol diet (HCHO) group demonstrated a 1.5-fold increase in myocardial protein oxidation compared with the normal diet (NORM) group, suggesting increased oxidative stress in these animals. (*p = 0.03.) The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions

9 Fig 8 Immunohistochemical localization of endostatin in the ischemic circumflex territory. Representative histologic sections of the ischemic territory of the normal diet (NORM) and the high-cholesterol diet (HCHO) groups. (A, B, C) Sections are from the NORM pigs. (D, E, F) Sections are from the HCHO pigs. Note the presence of endostatin (brown staining) in the coronary arterial wall (B, E) that is not present in the negative control (A, D). Endostatin is also present in the wall of smaller arterioles (C, F). The endostatin intensity in the vascular smooth muscle cell layers is clearly increased in the HCHO group compared with in the NORM. (Original magnification, ×200.) The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions


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