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Inhibition of neointimal hyperplasia by blocking αvβ3 integrin with a small peptide antagonist GpenGRGDSPCA*  Eric T. Choi, MD, Leslie Engel, PhD, Allan.

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Presentation on theme: "Inhibition of neointimal hyperplasia by blocking αvβ3 integrin with a small peptide antagonist GpenGRGDSPCA*  Eric T. Choi, MD, Leslie Engel, PhD, Allan."— Presentation transcript:

1 Inhibition of neointimal hyperplasia by blocking αvβ3 integrin with a small peptide antagonist GpenGRGDSPCA*  Eric T. Choi, MD, Leslie Engel, PhD, Allan D. Callow, MD, PhD, Shaping Sun, MMS, Jeffery Trachtenberg, MD, Sam Santoro, MD, PhD, Una S. Ryan, PhD  Journal of Vascular Surgery  Volume 19, Issue 1, Pages (January 1994) DOI: /S (94)70127-X Copyright © 1994 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

2 Fig. 1 Human aortic SMCs (1 x 104) were grown for 48 hours in presence of agar plugs with and without PDGF-AB (10 ng/ml). Journal of Vascular Surgery  , DOI: ( /S (94)70127-X) Copyright © 1994 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

3 Fig. 2 Microcatheter with longitudinal perforation was placed adjacent to distal half of rabbit common carotid artery after balloon injury. Alzet osmotic pump (model 2ML2) delivers 5 μl/hr for 14 days. Journal of Vascular Surgery  , DOI: ( /S (94)70127-X) Copyright © 1994 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

4 Fig. 3 Unstained, paraffin embedded cross-section of catheter (C) and artery (A) at site of delivery illustrate relative positions. Microcatheter is closely adjacent to artery without having physical contact. Peptide is delivered through hole (arrow) to be distributed in adjacent vessel wall. Journal of Vascular Surgery  , DOI: ( /S (94)70127-X) Copyright © 1994 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

5 Fig. 4 A, Human SMCs were stimulated with PDGF-AB from top. Human αvβ3 integrin staining was limited to leading edge. B, Without PDGF-AB stimulation, αvβ3 integrin was evenly distributed over bottom surface. Journal of Vascular Surgery  , DOI: ( /S (94)70127-X) Copyright © 1994 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

6 Fig. 5 LM609 ascites fluid was tested for its ability to block PDGF-AB–induced human SMC migration. Dilution of 1:100,000 significantly reduced SMC motility (vs control immunoglobin G1; asterisk represents p < 0.001; n = 4)). Journal of Vascular Surgery  , DOI: ( /S (94)70127-X) Copyright © 1994 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

7 Fig. 6 GpenGRGDSPCA had dose-dependent inhibition on human SMC motility (vs inactive peptide GRGESP; asterisk represents p < 0.01; double asterisk represents p < 0.005; n = 4). Journal of Vascular Surgery  , DOI: ( /S (94)70127-X) Copyright © 1994 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

8 Fig. 7 GpenGRGDSPCA had dose-dependent inhibition on rabbit SMC motility stimulated with PDGF-AB (vs GRGESP; asterisk represents p < 0.001; n = 4). Journal of Vascular Surgery  , DOI: ( /S (94)70127-X) Copyright © 1994 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

9 Fig. 8 Comparison of average neointimal area (mm2) among vehicle (n = 8), GRGESP (n = 7) and GpenGRGDSPCA (n = 8) groups (GpenGRGDSPCA vs GRGESP, asterisk represents p < 0.05; no significant difference between GRGESP and saline solution). Journal of Vascular Surgery  , DOI: ( /S (94)70127-X) Copyright © 1994 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

10 Fig. 9 Comparison of intima to media ratio showed significant difference between GpenGRGDSPCA and GRGESP (asterisk represents p < 0.01). No significant difference existed between GRGESP and saline solution. Journal of Vascular Surgery  , DOI: ( /S (94)70127-X) Copyright © 1994 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

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