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. 2000 Dec;20(12):2566- 2572.

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. 2000 Sep;20(9):2127-33] 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. 2000 May-Jun;37(3):170-82.] * P<0.05 vs. Ctrl

10. Tropoelastin gene expression Dist: Biphasic Prox: Increase Xu, Zarins, Glagov. J Vasc Surg. 2002 Sep;36(3):605-612Xu, Zarins, Glagov. Exp Mol Pathol. 2002 Apr;72(2):115-23 * 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. 2001 Mar;33(3):570-578 * 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