Collagen Turnover in Relation to Risk Factors and Hemodynamics in Human Intracranial Aneurysms
Abstract
Determinants for molecular and structural instability, that is, impending growth or rupture, of intracranial aneurysms (IAs) remain uncertain. To elucidate this, we endeavored to estimate the actual turnover rates of the main molecular constituent in human IA (collagen) on the basis of radiocarbon (14C) birth dating in relation to IA hemodynamics. Collagen turnover rates in excised human IA samples were calculated using mathematical modeling of 14C birth dating data of collagen in relation to risk factors and histological markers for collagen maturity/turnover in selected IA. Hemodynamics were simulated using image-based computational fluid dynamics. Correlation, logistic regression, and receiver operating characteristic analyses were performed. Collagen turnover rates were estimated in 46 IA (43 patients); computational fluid dynamics could be performed in 20 IA (20 patients). The mean collagen turnover rate (γ) constituted 126% (±1% error) per year. For patients with arterial hypertension, γ was greater than 2600% annually, whereas γ was distinctly lower with 32% (±1% error) per year for patients without risk factors, such as smoking and hypertension. There was a distinct association between histological presence of rather immature collagen in human IA and the presence of modifiable risk factors. Spatial-temporal averaged wall shear stress predicted rapid collagen turnover (oddsmore »
- Authors:
-
[1]
- University of Heidelberg, Mannheim (Germany)
- University at Buffalo, NY (United States)
- Westfalian Wilhelms-University, Münster (Germany)
- Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)
- University of California, Davis, CA (United States)
- University at Buffalo, NY (United States); Kaleida Health, Buffalo, NY (United States); Jacobs Institute, Buffalo, NY (United States)
- University of Toronto, ON (Canada)
- Publication Date:
- Research Org.:
- Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
- Sponsoring Org.:
- USDOE National Nuclear Security Administration (NNSA); National Institutes of Health (NIH); USDOE Laboratory Directed Research and Development (LDRD) Program
- OSTI Identifier:
- 1618823
- Report Number(s):
- LLNL-JRNL-787658
Journal ID: ISSN 0039-2499; 985555
- Grant/Contract Number:
- AC52-07NA27344; P41GM103483; R01NS091075
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Stroke
- Additional Journal Information:
- Journal Volume: 51; Journal Issue: 5; Journal ID: ISSN 0039-2499
- Publisher:
- American Heart Association
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES; logistic models; humans; intracranial aneurysm; collagen; risk factors; hemodynamics; birth dating; collagen turnover; wall shear stress
Citation Formats
Hackenberg, Katharina A. M., Rajabzadeh-Oghaz, Hamidreza, Dreier, Rita, Buchholz, Bruce A., Navid, Ali, Rocke, David M., Abdulazim, Amr, Hänggi, Daniel, Siddiqui, Adnan, Macdonald, R. Loch, Meng, Hui, and Etminan, Nima. Collagen Turnover in Relation to Risk Factors and Hemodynamics in Human Intracranial Aneurysms. United States: N. p., 2020.
Web. doi:10.1161/STROKEAHA.120.029335.
Hackenberg, Katharina A. M., Rajabzadeh-Oghaz, Hamidreza, Dreier, Rita, Buchholz, Bruce A., Navid, Ali, Rocke, David M., Abdulazim, Amr, Hänggi, Daniel, Siddiqui, Adnan, Macdonald, R. Loch, Meng, Hui, & Etminan, Nima. Collagen Turnover in Relation to Risk Factors and Hemodynamics in Human Intracranial Aneurysms. United States. https://doi.org/10.1161/STROKEAHA.120.029335
Hackenberg, Katharina A. M., Rajabzadeh-Oghaz, Hamidreza, Dreier, Rita, Buchholz, Bruce A., Navid, Ali, Rocke, David M., Abdulazim, Amr, Hänggi, Daniel, Siddiqui, Adnan, Macdonald, R. Loch, Meng, Hui, and Etminan, Nima. Fri .
"Collagen Turnover in Relation to Risk Factors and Hemodynamics in Human Intracranial Aneurysms". United States. https://doi.org/10.1161/STROKEAHA.120.029335. https://www.osti.gov/servlets/purl/1618823.
@article{osti_1618823,
title = {Collagen Turnover in Relation to Risk Factors and Hemodynamics in Human Intracranial Aneurysms},
author = {Hackenberg, Katharina A. M. and Rajabzadeh-Oghaz, Hamidreza and Dreier, Rita and Buchholz, Bruce A. and Navid, Ali and Rocke, David M. and Abdulazim, Amr and Hänggi, Daniel and Siddiqui, Adnan and Macdonald, R. Loch and Meng, Hui and Etminan, Nima},
abstractNote = {Determinants for molecular and structural instability, that is, impending growth or rupture, of intracranial aneurysms (IAs) remain uncertain. To elucidate this, we endeavored to estimate the actual turnover rates of the main molecular constituent in human IA (collagen) on the basis of radiocarbon (14C) birth dating in relation to IA hemodynamics. Collagen turnover rates in excised human IA samples were calculated using mathematical modeling of 14C birth dating data of collagen in relation to risk factors and histological markers for collagen maturity/turnover in selected IA. Hemodynamics were simulated using image-based computational fluid dynamics. Correlation, logistic regression, and receiver operating characteristic analyses were performed. Collagen turnover rates were estimated in 46 IA (43 patients); computational fluid dynamics could be performed in 20 IA (20 patients). The mean collagen turnover rate (γ) constituted 126% (±1% error) per year. For patients with arterial hypertension, γ was greater than 2600% annually, whereas γ was distinctly lower with 32% (±1% error) per year for patients without risk factors, such as smoking and hypertension. There was a distinct association between histological presence of rather immature collagen in human IA and the presence of modifiable risk factors. Spatial-temporal averaged wall shear stress predicted rapid collagen turnover (odds ratio, 1.6 [95% CI, 1.0–2.7]). Receiver operating characteristic analysis demonstrated a good test accuracy (area under the curve, 0.798 [95% CI, 0.598–0.998]) for average wall shear stress with a threshold ≥4.9 Pa for rapid collagen turnover. Our data indicate that turnover rates and stability of collagen in human IA are strongly associated with the presence of modifiable risk factors and aneurysmal hemodynamics. Finally, these findings underline the importance of strict risk factor modification in patients with unruptured IA. Future should include more detailed risk factor data to establish a more causal understanding of hemodynamics and the rupture risk of individual IA.},
doi = {10.1161/STROKEAHA.120.029335},
journal = {Stroke},
number = 5,
volume = 51,
place = {United States},
year = {Fri Mar 20 00:00:00 EDT 2020},
month = {Fri Mar 20 00:00:00 EDT 2020}
}
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