Notes
Slide Show
Outline
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Effect of Shear Level on Extent and Nature of Resistance Artery Remodeling
  • Joseph L. Unthank, Ph.D.
  • Professor, Departments of Surgery, and Cellular and Integrative Physiology , Indiana University Medical Center, Indianapolis, Indiana


  • Presented at the 7th International Symposium on Resistance Arteries, Session on Flow Related Vascular Remodeling. Muskoka Sands, Ontario Canada, 7/5/2001
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3 Major Remodeling Processes
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Why Study Shear Level?
  • Why is shear-mediated remodeling impaired with maturation?
  • Why does the initial stage of collateral development involve increases in wall area in some but not all cases--is the nature of the remodeling dependent upon shear level??
  • Is the rate of luminal change dependent upon shear level?
  • Why is collateral development impaired in models of endothelial dysfunction?
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COLLATERAL DEVELOPMENT
  •  EXTENT
    • Magnitude
    • Rate


  • NATURE
    • Wall areas
    • Cellular Growth
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Model 1
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# Intimal Nuclei
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# Medial Nuclei
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COLLATERAL DEVELOPMENT
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WORKING HYPOTHESES: 

1. Both the rate and magnitude of luminal expansion is dependent upon the degree of initial shear elevation
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WORKING HYPOTHESES: 

2.  Specific remodeling events within the arterial wall layers depend upon the level of shear alteration
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WORKING HYPOTHESES: 

3. Shear level dependent remodeling events  are mediated by alterations in the balance of  growth modulators
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MODEL 2: Multiple Shear Levels
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MODEL 3: Multiple Shear Levels
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Blood Flow and Wall Shear Rate
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% Diameter Change
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Rate of Diameter Change
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Intimal Area
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Medial Area
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3-D METHOD
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Endothelial Nuclear Density
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Medial Nuclear Density
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Adventitial Nuclear Density
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Cellular Proliferation (Ki-67)
200%                      400%
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eNOS Staining
100%                       400%
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eNOS Content
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COLLATERAL DEVELOPMENT
Shear-Dependent Alterations
  •  EXTENT
    • Magnitude
    • Rate


  •   Balance of Growth Modulators


  • NATURE
    • Wall areas
    • Cellular Growth
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Shear-Mediated Collateral Growth
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Schematic
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Collaborators
  • Jay L. Tuttle, Ph.D.
  • Ryan D. Nachreiner, M.D.
  • Amardip S. Bhuller, M.D.
  • Kevin W. Condict, B.S.
  • Bret A. Connors, Ph.D.



  • B. Paul Herring, Ph.D.
  • Michael C. Dalsing, M.D.
  • Sharon Bledsoe, B.S.
  • Jennifer Stashevsky