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Chengpei Xu, MD, PhD Hemodynamics and Vascular Remodeling Symposium In Honor of Dr. Seymour Glagov Thursday February 20, 2003.

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Presentation on theme: "Chengpei Xu, MD, PhD Hemodynamics and Vascular Remodeling Symposium In Honor of Dr. Seymour Glagov Thursday February 20, 2003."— Presentation transcript:

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2 Chengpei Xu, MD, PhD Hemodynamics and Vascular Remodeling Symposium In Honor of Dr. Seymour Glagov Thursday February 20, 2003

3 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 (Lyon, Runyon-Hass, Davis, Glagov and Zarins. JVS, 5(1):59-67, 1987)  75% lumen reduction

4 Aortic wall structure

5 Characteristics of wall motion

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

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

8 Reduction of aortic wall motion inhibits hypertension-mediated experimental atherosclerosis No wrap Loose wrap Firm wrap Control

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

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

11 Collage type ICollage type IIITropoelastin Differential distribution of major ECM at the Proximal

12 TGF-  1 and  3 genes upregulated * Molecular Bases in Vessel Remodeling (2) Xu, Lee, Singh, Sho, Li, Sho, Masuda, Zarins. J Vasc Surg Mar;33(3): * P<0.05 vs. Ctrl

13 Cell proliferationBrdU incorporation rate increased * P<0.05 vs. Ctrl

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

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

16 Wall thickness increased * P<0.05 vs. Ctrl

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

18 * * *

19 Immuno-fluorescence staining of PDGF-A

20 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


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