Abstract | INTRODUCTION: METHODS:
Elastase-induced aneurysms were created at the origin of the right common carotid artery in rabbits. Hemodynamic parameters were estimated using computational fluid dynamic simulations based on 3-D-reconstructed models of the vasculature. Expression of matrix metalloproteinases ( MMPs), their inhibitors (TIMPs) and markers of vascular remodeling were measured in different spatial regions within the aneurysms. RESULTS: Altered expression of biological markers relative to controls was correlated with the locations of subnormal time-averaged wall shear stress (WSS) but not with the magnitude of pressure. In the aneurysms, WSS was low and expression of biological markers was significantly altered in a time-dependent fashion. At 2 weeks, an upregulation of active-MMP-2, downregulation of TIMP-1 and TIMP-2, and intact endothelium were found in aneurysm cavities. However, by 12 weeks, endothelial cells were absent or scattered, and levels of pro- and active-MMP-2 were not different from those in control arteries, but pro-MMP-9 and both TIMPs were upregulated. CONCLUSION: These results reveal a strong, spatially localized correlation between diminished WSS and differential expression of biological markers of vascular remodeling in elastase-induced saccular aneurysms. The ability of the wall to function and maintain a healthy endothelium in a low shear environment appears to be significantly impaired by chronic exposure to low WSS.
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Authors | Ramanathan Kadirvel, Yong-Hong Ding, Daying Dai, Hasballah Zakaria, Anne M Robertson, Mark A Danielson, Debra A Lewis, Harry J Cloft, David F Kallmes |
Journal | Neuroradiology
(Neuroradiology)
Vol. 49
Issue 12
Pg. 1041-53
(Dec 2007)
ISSN: 0028-3940 [Print] Germany |
PMID | 17882410
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Biomarkers
- Contrast Media
- Matrix Metalloproteinase Inhibitors
- Iohexol
- Pancreatic Elastase
- Matrix Metalloproteinases
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Topics |
- Angiography, Digital Subtraction
- Animals
- Biomarkers
(blood)
- Blood Flow Velocity
- Blotting, Western
- Computer Simulation
- Contrast Media
- Hemorheology
- Imaging, Three-Dimensional
- Immunohistochemistry
- Intracranial Aneurysm
(blood, diagnostic imaging, physiopathology)
- Iohexol
- Matrix Metalloproteinase Inhibitors
- Matrix Metalloproteinases
(blood)
- Microscopy, Electron, Scanning
- Pancreatic Elastase
- Pulsatile Flow
- Rabbits
- Shear Strength
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