Chengpei Xu, MD, PhD

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

• Aortic Coarctation-Induced
• Vascular Wall Remodeling

• Chengpei Xu, MD, PhD

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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)
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Aortic wall structure
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Characteristics of wall motion
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Lyon, Runyon-Hass, Davis, Glagov and Zarins.
JVS, 5(1)59-67, 1987
Xu, Zarins, Pannaraj, Bassiouny, Glagov.
Arterioscler Thromb Vasc Biol. 2000
Dec20(12)2566-2572.
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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 Sep20(9)2127-33
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Reduction of aortic wall motion
inhibitshypertension-mediated experimental
atherosclerosis
No wrap
Loose wrap
Control
Firm wrap
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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
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Tropoelastin gene expression
Prox Increase
Dist Biphasic
Plt0.05 vs. Ctrl
Plt0.05 vs. Ctrl
Xu, Zarins, Glagov. J Vasc Surg. 2002
Sep36(3)605-612
Xu, Zarins, Glagov. Exp Mol Pathol. 2002
Apr72(2)115-23
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Differential distribution of major ECM at the
Proximal
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Molecular Bases in Vessel Remodeling (2)
TGF-b1 and b3 genes upregulated


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Cell proliferation
BrdU incorporation rate increased
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Some apoptosis related cytokines - decreased
expression


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Apoptosis detected LSCM, All nuclei were stained
red with PI, and the nuclei of apoptotic cells
were labeled green
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Wall thickness increased
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PDGF-A expression upregulated
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(No Transcript)
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Immuno-fluorescence staining of PDGF-A
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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