The influence of hemodynamic forces on biomarkers in the walls of elastase-induced aneurysms in rabbits

• Published in: Neuroradiology 2007-12, Vol.49 (12), p.1041-1053
• Main Authors: KADIRVEL, Ramanathan, DING, Yong-Hong, DAYING DAI, ZAKARIA, Hasballah, ROBERTSON, Anne M, DANIELSON, Mark A, LEWIS, Debra A, CLOFT, Harry J, KALLMES, David F
• Format: Article
• Language: English
• Subjects: Aneurysms; Angiography, Digital Subtraction; Animals; Biological and medical sciences; Biomarkers - blood; Blood Flow Velocity; Blotting, Western; Computer Simulation; Contrast Media; Electrodiagnosis. Electric activity recording; Fluid dynamics; Hemorheology; Imaging, Three-Dimensional; Immunohistochemistry; Intracranial Aneurysm - blood; Intracranial Aneurysm - diagnostic imaging; Intracranial Aneurysm - physiopathology; Investigative techniques, diagnostic techniques (general aspects); Iohexol; Matrix Metalloproteinase Inhibitors; Matrix Metalloproteinases - blood; Medical sciences; Microscopy, Electron, Scanning; Nervous system; Neurology; Pancreatic Elastase; Pulsatile Flow; Rabbits; Radiodiagnosis. Nmr imagery. Nmr spectrometry; Radiology; Shear Strength; Shear stress; Simulation
• ISSN: 0028-3940; 1432-1920
• DOI: 10.1007/s00234-007-0295-0

Biological and biophysical factors have been shown to play an important role in the initiation, progression, and rupture of intracranial aneurysms. The purpose of this study was to evaluate the association between hemodynamic forces and markers of vascular remodeling in elastase-induced saccular aneurysms in rabbits. 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. 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. 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.