Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Increased Collagen I/ Collagen III Ratio Is Associated with Hemorrhage in Brain Arteriovenous Malformations in Human and Mouse

Zahra Shabani
,
Joana Schurger
,
Xiaonan Zhu
,
Chaoliang Tang
,
Li Ma
ORCID logo ,
Alka Yadav
,
Rich Liang
,
Kelly Press
,
Shantel Weinsheimer
,
Annika Schmidt
,
Calvin Wang
,
Abinav Sekhar
,
Helen Kim
,
hua su
* ORCID logo
Version 1 : Received: 6 December 2023 / Approved: 6 December 2023 / Online: 6 December 2023 (10:36:46 CET)

A peer-reviewed article of this Preprint also exists.

Shabani, Z.; Schuerger, J.; Zhu, X.; Tang, C.; Ma, L.; Yadav, A.; Liang, R.; Press, K.; Weinsheimer, S.; Schmidt, A.; Wang, C.; Sekhar, A.; Nelson, J.; Kim, H.; Su, H. Increased Collagen I/Collagen III Ratio Is Associated with Hemorrhage in Brain Arteriovenous Malformations in Human and Mouse. Cells 2024, 13, 92. Shabani, Z.; Schuerger, J.; Zhu, X.; Tang, C.; Ma, L.; Yadav, A.; Liang, R.; Press, K.; Weinsheimer, S.; Schmidt, A.; Wang, C.; Sekhar, A.; Nelson, J.; Kim, H.; Su, H. Increased Collagen I/Collagen III Ratio Is Associated with Hemorrhage in Brain Arteriovenous Malformations in Human and Mouse. Cells 2024, 13, 92.

Abstract

Background: Increase of collagen I (COL I)/COL III ratio enhances vessel wall stiffness and renders vessels less resistant to blood flow and pressure changes. We hypothesized that COL I/COL III ratio is increased in the brain arteriovenous malformations (bAVMs), which is associated with bAVM hemorrhage. Method: Surgically resected human bAVM samples and mouse bAVMs induced in three transgenic mouse lines with activin receptor-like kinase 1 or endoglin deletion in the endothelial cells or in the brain focally. Colony-stimulating factor receptor inhibitor was used to transiently deplete microglia. COL I and COL III levels, hemorrhage, and gene expression in bAVMs were analyzed. Results: The COL I and COL III levels and the COL I/COL III ratio were higher on human and mouse bAVMs than controls, which was associated with bAVM hemorrhage. Col I and Col III mRNAs were also increased in mouse bAVMs. The degree of microhemorrhage in mouse bAVMs was positively correlated with Col I/Col III ratios. Transient depletion of microglia reduced Col I/Col III ratio and microhemorrhage in mouse bAVMs. Conclusion: COL I/COL III ratio are increased in bAVM vessels, which is associated with bAVM hemorrhage. Depletion of microglia reduces Col I/Col III ratio and hemorrhage in mice bAVMs.

Keywords

Brain arteriovenous malformation; Collagen I; Collagen III; Microhemorrhage; Depletion of microglia; Gluycoprotein nonmetastatic B

Subject

Biology and Life Sciences, Other

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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