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Inhibitory Effects of Calcitonin Gene-Related Peptides on Experimental Vein Graft Disease  Xiaoning Zhang, MD, Jian Zhuang, MD, Hongsui Wu, MB, Zhihong.

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Presentation on theme: "Inhibitory Effects of Calcitonin Gene-Related Peptides on Experimental Vein Graft Disease  Xiaoning Zhang, MD, Jian Zhuang, MD, Hongsui Wu, MB, Zhihong."— Presentation transcript:

1 Inhibitory Effects of Calcitonin Gene-Related Peptides on Experimental Vein Graft Disease 
Xiaoning Zhang, MD, Jian Zhuang, MD, Hongsui Wu, MB, Zhihong Chen, MM, Jian Su, MM, Shiliang Chen, MB, Jianguang Chen, MB  The Annals of Thoracic Surgery  Volume 90, Issue 1, Pages (July 2010) DOI: /j.athoracsur Copyright © 2010 The Society of Thoracic Surgeons Terms and Conditions

2 Fig 1 Gene expression in vein grafts. (A) Expression of calcitonin gene-related peptide (CGRP) ribonucleic acid at 4 weeks in the mosaic adeno-associated virus vectors containing CGRP gene (AAV2/1.CGRP) group vein grafts. The total ribonucleic acid extracted from the AAV2/1.CGRP group, the mosaic adeno-associated virus vectors containing Escherichia coli B-galactosidase gene (AAV2/1.LacZ) group, and the saline group vein grafts are shown, with AAV2/1.CGRP as the positive control and saline as the negative control. The AAV2/1.CGRP group and AAV2/1.CGRP are depicted here with positive matches for CGRP. Polymerase chain reaction complementary deoxyribonucleic acid products were visualized on agarose gels stained with ethidium bromide. (B) Cross-sectional view of AAV2/1.LacZ group vein grafts. Dark blue inclusions demonstrate β-galactosidase staining (original magnification, ×400). The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2010 The Society of Thoracic Surgeons Terms and Conditions

3 Fig 2 Effect of transfection of calcitonin gene-related peptide (CGRP) on neointimal hyperplasia in vein grafts at 4 weeks after surgery. (A) Representative histologic sections of vein grafts stained with elastic van Gieson's stain (EVG; magnification ×100). (B) Ratio of intimal to medial area at 4 weeks after vein grafting with gene transfer of mosaic adeno-associated virus vectors containing calcitonin gene-related peptide gene (AAV2/1.CGRP), mosaic adeno-associated virus vectors containing Escherichia coli B-galactosidase gene (AAV2/1.LacZ), and saline are shown. Values shown are the mean ± standard error of the mean. *p < The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2010 The Society of Thoracic Surgeons Terms and Conditions

4 Fig 3 Histopathologic and immunohistochemical findings in rabbit vein grafts. (A) In vein grafts from the mosaic adeno-associated virus vectors containing calcitonin gene-related peptide gene (AAV2/1.CGRP) group, the muscularis and intima were intact. In vein grafts from the mosaic adeno-associated virus vectors containing Escherichia coli B-galactosidase gene (AAV2/1.LacZ) and saline groups, the intima exhibited hyperplasia until complete occlusion. (B) The AAV2/1.CGRP group vein grafts exhibited minimal inflammation, but inflammatory cells infiltrated all layers of the vein grafts of the AAV2/1.LacZ and saline groups. (C) Immunohistochemical studies with a monoclonal antibody CD68 specific for macrophages demonstrated minimal macrophage immunostaining in AAV2/1.CGRP group vein grafts; high-level expression of macrophages in the endothelium and adventitia of AAV2/1.LacZ group and saline group vein grafts was observed. The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2010 The Society of Thoracic Surgeons Terms and Conditions

5 Fig 4 Mean messenger ribonucleic acid (mRNA) levels of inflammation-mediating molecules in vein grafts from mosaic adeno-associated virus vectors containing calcitonin gene-related peptide gene (AAV2/1.CGRP), mosaic adeno-associated virus vectors containing Escherichia coli B-galactosidase gene (AAV2/1.LacZ), and saline groups were evaluated by quantitative real-time polymerase chain reaction using glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as an internal standard. Each specific inflammation-mediating molecule is indicated as follows: (A) monocyte chemoattractant protein-1 (MCP-1); (B) tumor necrosis factor-α (TNF-α); (C) inducible nitric oxide synthase (iNOS); and (D) matrix metalloproteinase-9 (MMP-9). *p < 0.05, AAV2/1.CGRP group versus AAV2/1.LacZ and saline groups (n = 7 per group). The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2010 The Society of Thoracic Surgeons Terms and Conditions

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