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

<b>Background:</b> The increase in the collagen I (COL I)/COL III ratio enhances vessel wall stiffness and renders vessels less resistant to blood flow and pressure changes. Activated microglia enhance inflammation-induced fibrosis. <b>Hypotheses:</b> The COL I/COL III ratio...

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Main Authors: Zahra Shabani, Joana Schuerger, Xiaonan Zhu, Chaoliang Tang, Li Ma, Alka Yadav, Rich Liang, Kelly Press, Shantel Weinsheimer, Annika Schmidt, Calvin Wang, Abinav Sekhar, Jeffrey Nelson, Helen Kim, Hua Su
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Language:English
Published: MDPI AG 2024-01-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/13/1/92
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author Zahra Shabani
Joana Schuerger
Xiaonan Zhu
Chaoliang Tang
Li Ma
Alka Yadav
Rich Liang
Kelly Press
Shantel Weinsheimer
Annika Schmidt
Calvin Wang
Abinav Sekhar
Jeffrey Nelson
Helen Kim
Hua Su
author_facet Zahra Shabani
Joana Schuerger
Xiaonan Zhu
Chaoliang Tang
Li Ma
Alka Yadav
Rich Liang
Kelly Press
Shantel Weinsheimer
Annika Schmidt
Calvin Wang
Abinav Sekhar
Jeffrey Nelson
Helen Kim
Hua Su
author_sort Zahra Shabani
collection DOAJ
description <b>Background:</b> The increase in the collagen I (COL I)/COL III ratio enhances vessel wall stiffness and renders vessels less resistant to blood flow and pressure changes. Activated microglia enhance inflammation-induced fibrosis. <b>Hypotheses:</b> The COL I/COL III ratio in human and mouse brain arteriovenous malformations (bAVMs) is associated with bAVM hemorrhage, and the depletion of microglia decreases the COL I/COL III ratio and hemorrhage. <b>Method:</b> COL I, COL III, and hemorrhages were analyzed in 12 human bAVMs and 6 control brains, and mouse bAVMs induced in three mouse lines with activin receptor-like kinase 1 (<i>n</i> = 7) or endoglin (<i>n</i> = 7) deleted in the endothelial cells or brain focally (<i>n</i> = 5). The controls for the mouse study were no-gene-deleted litter mates. Mouse bAVMs were used to test the relationships between the Col I/Col III ratio and hemorrhage and whether the transient depletion of microglia reduces the Col I/Col III ratio and hemorrhage. <b>Results:</b> The COL I/COL III ratio was higher in the human and mouse bAVMs than in controls. The microhemorrhage in mouse bAVMs was positively correlated with the Col I/Col III ratio. Transient depletion of microglia reduced the Col I/Col III ratio and microhemorrhage. <b>Conclusions:</b> The COL I/COL III ratio in the bAVMs was associated with bAVM hemorrhage. The depletion of microglia reduced the bAVM Col I/Col III ratio and hemorrhage.
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spelling doaj.art-f8a5d4898637431194463104c0117eea2024-01-10T14:53:30ZengMDPI AGCells2073-44092024-01-011319210.3390/cells13010092Increased Collagen I/Collagen III Ratio Is Associated with Hemorrhage in Brain Arteriovenous Malformations in Human and MouseZahra Shabani0Joana Schuerger1Xiaonan Zhu2Chaoliang Tang3Li Ma4Alka Yadav5Rich Liang6Kelly Press7Shantel Weinsheimer8Annika Schmidt9Calvin Wang10Abinav Sekhar11Jeffrey Nelson12Helen Kim13Hua Su14Center for Cerebrovascular Research, University of California, San Francisco, CA 94143, USACenter for Cerebrovascular Research, University of California, San Francisco, CA 94143, USACenter for Cerebrovascular Research, University of California, San Francisco, CA 94143, USACenter for Cerebrovascular Research, University of California, San Francisco, CA 94143, USACenter for Cerebrovascular Research, University of California, San Francisco, CA 94143, USACenter for Cerebrovascular Research, University of California, San Francisco, CA 94143, USACenter for Cerebrovascular Research, University of California, San Francisco, CA 94143, USACenter for Cerebrovascular Research, University of California, San Francisco, CA 94143, USACenter for Cerebrovascular Research, University of California, San Francisco, CA 94143, USACenter for Cerebrovascular Research, University of California, San Francisco, CA 94143, USACenter for Cerebrovascular Research, University of California, San Francisco, CA 94143, USACenter for Cerebrovascular Research, University of California, San Francisco, CA 94143, USACenter for Cerebrovascular Research, University of California, San Francisco, CA 94143, USACenter for Cerebrovascular Research, University of California, San Francisco, CA 94143, USACenter for Cerebrovascular Research, University of California, San Francisco, CA 94143, USA<b>Background:</b> The increase in the collagen I (COL I)/COL III ratio enhances vessel wall stiffness and renders vessels less resistant to blood flow and pressure changes. Activated microglia enhance inflammation-induced fibrosis. <b>Hypotheses:</b> The COL I/COL III ratio in human and mouse brain arteriovenous malformations (bAVMs) is associated with bAVM hemorrhage, and the depletion of microglia decreases the COL I/COL III ratio and hemorrhage. <b>Method:</b> COL I, COL III, and hemorrhages were analyzed in 12 human bAVMs and 6 control brains, and mouse bAVMs induced in three mouse lines with activin receptor-like kinase 1 (<i>n</i> = 7) or endoglin (<i>n</i> = 7) deleted in the endothelial cells or brain focally (<i>n</i> = 5). The controls for the mouse study were no-gene-deleted litter mates. Mouse bAVMs were used to test the relationships between the Col I/Col III ratio and hemorrhage and whether the transient depletion of microglia reduces the Col I/Col III ratio and hemorrhage. <b>Results:</b> The COL I/COL III ratio was higher in the human and mouse bAVMs than in controls. The microhemorrhage in mouse bAVMs was positively correlated with the Col I/Col III ratio. Transient depletion of microglia reduced the Col I/Col III ratio and microhemorrhage. <b>Conclusions:</b> The COL I/COL III ratio in the bAVMs was associated with bAVM hemorrhage. The depletion of microglia reduced the bAVM Col I/Col III ratio and hemorrhage.https://www.mdpi.com/2073-4409/13/1/92brain arteriovenous malformationcollagen Icollagen IIImicrohemorrhagedepletion of microgliagluycoprotein nonmetastatic B
spellingShingle Zahra Shabani
Joana Schuerger
Xiaonan Zhu
Chaoliang Tang
Li Ma
Alka Yadav
Rich Liang
Kelly Press
Shantel Weinsheimer
Annika Schmidt
Calvin Wang
Abinav Sekhar
Jeffrey Nelson
Helen Kim
Hua Su
Increased Collagen I/Collagen III Ratio Is Associated with Hemorrhage in Brain Arteriovenous Malformations in Human and Mouse
Cells
brain arteriovenous malformation
collagen I
collagen III
microhemorrhage
depletion of microglia
gluycoprotein nonmetastatic B
title Increased Collagen I/Collagen III Ratio Is Associated with Hemorrhage in Brain Arteriovenous Malformations in Human and Mouse
title_full Increased Collagen I/Collagen III Ratio Is Associated with Hemorrhage in Brain Arteriovenous Malformations in Human and Mouse
title_fullStr Increased Collagen I/Collagen III Ratio Is Associated with Hemorrhage in Brain Arteriovenous Malformations in Human and Mouse
title_full_unstemmed Increased Collagen I/Collagen III Ratio Is Associated with Hemorrhage in Brain Arteriovenous Malformations in Human and Mouse
title_short Increased Collagen I/Collagen III Ratio Is Associated with Hemorrhage in Brain Arteriovenous Malformations in Human and Mouse
title_sort increased collagen i collagen iii ratio is associated with hemorrhage in brain arteriovenous malformations in human and mouse
topic brain arteriovenous malformation
collagen I
collagen III
microhemorrhage
depletion of microglia
gluycoprotein nonmetastatic B
url https://www.mdpi.com/2073-4409/13/1/92
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