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Chengpei Xu, MD, PhD

Hemodynamics and Vascular Remodeling Symposium In Honor of Dr. Seymour Glagov Thursday February 20, 2003. Chengpei Xu, MD, PhD. Aortic Coarctation-Induced Vascular Wall Remodeling. Introduction. Vascular wall responds to hemodynamic alteration

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Chengpei Xu, MD, PhD

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  1. Hemodynamics and Vascular Remodeling Symposium In Honor of Dr. Seymour Glagov Thursday February 20, 2003 Chengpei Xu, MD, PhD Aortic Coarctation-Induced Vascular Wall Remodeling

  2. Introduction • Vascular wall responds to hemodynamic alteration • Hypertension induces vascular wall remodeling • Aortic coarctation results in •  Bp,  wall motion,  wall thickening, lesion prone Proximally • Bp, Complex wall motion, PSD, lesion resistant Distally 75% lumen reduction (Lyon, Runyon-Hass, Davis, Glagov and Zarins.JVS, 5(1):59-67, 1987)

  3. Aortic wall structure

  4. Characteristics of wall motion

  5. Lyon, Runyon-Hass, Davis, Glagov and Zarins.JVS, 5(1):59-67, 1987 Xu, Zarins, Pannaraj, Bassiouny, Glagov. Arterioscler Thromb Vasc Biol. 2000 Dec;20(12):2566-2572.

  6. Reduction of aortic wall motion by wrapping the aorta in rabbits Levels A B C D Materials and Methods Coarctation + PTFE wrapping + diet Wall motion by ultrasound system Wall motion=% of  lumen at A, B, C, D Section Firm wrap loose wrap [Tropea and Zarins et al. Arterioscler Thromb Vasc Biol. 2000 Sep;20(9):2127-33]

  7. Reduction of aortic wall motion inhibitshypertension-mediated experimental atherosclerosis No wrap Loose wrap Control Firm wrap

  8. Collagen type I Collagen type III *P<0.05 vs. Ctrl *P<0.05 vs. Ctrl [Xu, Zarins, Bassiouny, Briggs, Reardon, Glagov. J Vasc Res. 2000 May-Jun;37(3):170-82.] Molecular mechanisms in the coarctation induced remodeling (1) Prox: Up regulation of gene expression for collagen types I and III Dist: At the PSD, gene expression for collagen was not remarkable

  9. Tropoelastin gene expression Prox: Increase Dist: Biphasic *P<0.05 vs. Ctrl *P<0.05 vs. Ctrl Xu, Zarins, Glagov. Exp Mol Pathol. 2002 Apr;72(2):115-23 Xu, Zarins, Glagov. J Vasc Surg. 2002 Sep;36(3):605-612

  10. Collage type I Collage type III Tropoelastin Differential distribution of major ECM at the Proximal

  11. *P<0.05 vs. Ctrl *P<0.05 vs. Ctrl Xu, Lee, Singh, Sho, Li, Sho, Masuda, Zarins. J Vasc Surg. 2001 Mar;33(3):570-578 Molecular Bases in Vessel Remodeling (2) TGF-b1 and b3 genes upregulated *

  12. *P<0.05 vs. Ctrl Cell proliferation BrdU incorporation rate increased

  13. *P<0.05 vs. Ctrl *P<0.05 vs. Ctrl Some apoptosis related cytokines - decreased expression

  14. *P<0.05 vs. Ctrl Apoptosis detected LSCM, All nuclei were stained red with PI, and the nuclei of apoptotic cells were labeled green

  15. *P<0.05 vs. Ctrl Wall thickness increased

  16. * * * * P<0.05 vs. Ctrl PDGF-A expression upregulated

  17. * * * * P<0.05 vs. Ctrl

  18. Immuno-fluorescence staining of PDGF-A

  19. Summary Coarctation-induced remodeling involves:  Wall motion - accelerating atherosclerosis • ECM gene expression & differential deposition Tropoelastin regulation more at the PSD A coordinated regulation of cell proliferation and cell death, governing the remodeling Thank You

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