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

Ramanathan D Kadirvel, Yong Hong Ding, Daying Dai, Hasballah Zakaria, Anne M. Robertson, Mark A. Danielson, Debra A. Lewis, Harry J. Cloft, David F Kallmes

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Introduction: 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. 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.

Original languageEnglish (US)
Pages (from-to)1041-1053
Number of pages13
JournalNeuroradiology
Volume49
Issue number12
DOIs
StatePublished - Dec 2007

Fingerprint

Pancreatic Elastase
Aneurysm
Biomarkers
Hemodynamics
Rabbits
Matrix Metalloproteinase 2
Endothelium
Tissue Inhibitor of Metalloproteinase-2
Tissue Inhibitor of Metalloproteinase-1
Matrix Metalloproteinase Inhibitors
Common Carotid Artery
Biological Factors
Intracranial Aneurysm
Hydrodynamics
Rupture
Up-Regulation
Down-Regulation
Endothelial Cells
Arteries
Pressure

Keywords

  • Aneurysm
  • Hemodynamics
  • Matrix metalloproteinases
  • Shear stress

ASJC Scopus subject areas

  • Clinical Neurology
  • Radiology Nuclear Medicine and imaging
  • Radiological and Ultrasound Technology

Cite this

The influence of hemodynamic forces on biomarkers in the walls of elastase-induced aneurysms in rabbits. / Kadirvel, Ramanathan D; Ding, Yong Hong; Dai, Daying; Zakaria, Hasballah; Robertson, Anne M.; Danielson, Mark A.; Lewis, Debra A.; Cloft, Harry J.; Kallmes, David F.

In: Neuroradiology, Vol. 49, No. 12, 12.2007, p. 1041-1053.

Research output: Contribution to journalArticle

Kadirvel, RD, Ding, YH, Dai, D, Zakaria, H, Robertson, AM, Danielson, MA, Lewis, DA, Cloft, HJ & Kallmes, DF 2007, 'The influence of hemodynamic forces on biomarkers in the walls of elastase-induced aneurysms in rabbits', Neuroradiology, vol. 49, no. 12, pp. 1041-1053. https://doi.org/10.1007/s00234-007-0295-0
Kadirvel, Ramanathan D ; Ding, Yong Hong ; Dai, Daying ; Zakaria, Hasballah ; Robertson, Anne M. ; Danielson, Mark A. ; Lewis, Debra A. ; Cloft, Harry J. ; Kallmes, David F. / The influence of hemodynamic forces on biomarkers in the walls of elastase-induced aneurysms in rabbits. In: Neuroradiology. 2007 ; Vol. 49, No. 12. pp. 1041-1053.
@article{0a80189fe3db43f88794c5401044e7f1,
title = "The influence of hemodynamic forces on biomarkers in the walls of elastase-induced aneurysms in rabbits",
abstract = "Introduction: 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. 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.",
keywords = "Aneurysm, Hemodynamics, Matrix metalloproteinases, Shear stress",
author = "Kadirvel, {Ramanathan D} and Ding, {Yong Hong} and Daying Dai and Hasballah Zakaria and Robertson, {Anne M.} and Danielson, {Mark A.} and Lewis, {Debra A.} and Cloft, {Harry J.} and Kallmes, {David F}",
year = "2007",
month = "12",
doi = "10.1007/s00234-007-0295-0",
language = "English (US)",
volume = "49",
pages = "1041--1053",
journal = "Neuroradiology",
issn = "0028-3940",
publisher = "Springer Verlag",
number = "12",

}

TY - JOUR

T1 - The influence of hemodynamic forces on biomarkers in the walls of elastase-induced aneurysms in rabbits

AU - Kadirvel, Ramanathan D

AU - Ding, Yong Hong

AU - Dai, Daying

AU - Zakaria, Hasballah

AU - Robertson, Anne M.

AU - Danielson, Mark A.

AU - Lewis, Debra A.

AU - Cloft, Harry J.

AU - Kallmes, David F

PY - 2007/12

Y1 - 2007/12

N2 - Introduction: 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. 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.

AB - Introduction: 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. 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.

KW - Aneurysm

KW - Hemodynamics

KW - Matrix metalloproteinases

KW - Shear stress

UR - http://www.scopus.com/inward/record.url?scp=36349031792&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=36349031792&partnerID=8YFLogxK

U2 - 10.1007/s00234-007-0295-0

DO - 10.1007/s00234-007-0295-0

M3 - Article

C2 - 17882410

AN - SCOPUS:36349031792

VL - 49

SP - 1041

EP - 1053

JO - Neuroradiology

JF - Neuroradiology

SN - 0028-3940

IS - 12

ER -