Biology of cerebral arteriovenous malformations with a focus on inflammation

Nikolaos Mouchtouris; Pascal M Jabbour; Robert M Starke; David M Hasan; Mario Zanaty; Thana Theofanis; Dale Ding; Stavropoula I Tjoumakaris; Aaron S Dumont; George M Ghobrial; David Kung; Robert H Rosenwasser; Nohra Chalouhi

doi:10.1038/jcbfm.2014.179

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Biology of cerebral arteriovenous malformations with a focus on inflammation

Journal article

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Peer reviewed

Biology of cerebral arteriovenous malformations with a focus on inflammation

Nikolaos Mouchtouris, Pascal M Jabbour, Robert M Starke, David M Hasan, Mario Zanaty, Thana Theofanis, Dale Ding, Stavropoula I Tjoumakaris, Aaron S Dumont, George M Ghobrial, …

Journal of cerebral blood flow and metabolism, Vol.35(2), pp.167-175

02/2015

DOI: 10.1038/jcbfm.2014.179

PMCID: PMC4426734

PMID: 25407267

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Abstract

Cerebral arteriovenous malformations (AVMs) entail a significant risk of intracerebral hemorrhage owing to the direct shunting of arterial blood into the venous vasculature without the dissipation of the arterial blood pressure. The mechanisms involved in the growth, progression and rupture of AVMs are not clearly understood, but a number of studies point to inflammation as a major contributor to their pathogenesis. The upregulation of proinflammatory cytokines induces the overexpression of cell adhesion molecules in AVM endothelial cells, resulting in enhanced recruitment of leukocytes. The increased leukocyte-derived release of metalloproteinase-9 is known to damage AVM walls and lead to rupture. Inflammation is also involved in altering the AVM angioarchitecture via the upregulation of angiogenic factors that affect endothelial cell proliferation, migration and apoptosis. The effects of inflammation on AVM pathogenesis are potentiated by certain single-nucleotide polymorphisms in the genes of proinflammatory cytokines, increasing their protein levels in the AVM tissue. Furthermore, studies on metalloproteinase-9 inhibitors and on the involvement of Notch signaling in AVMs provide promising data for a potential basis for pharmacological treatment of AVMs. Potential therapeutic targets and areas requiring further investigation are highlighted.

Inflammation - pathology

Leukocytes - pathology

Cell Adhesion Molecules - genetics

Matrix Metalloproteinase 9 - biosynthesis

Endothelial Cells - metabolism

Receptors, Notch - metabolism

Humans

Intracranial Arteriovenous Malformations - drug therapy

Receptors, Notch - genetics

Signal Transduction - genetics

Cell Adhesion Molecules - metabolism

Intracranial Arteriovenous Malformations - pathology

Intracranial Arteriovenous Malformations - metabolism

Up-Regulation - drug effects

Inflammation - metabolism

Animals

Inflammation - drug therapy

Matrix Metalloproteinase 9 - genetics

Intracranial Arteriovenous Malformations - genetics

Inflammation - genetics

Polymorphism, Single Nucleotide

Endothelial Cells - pathology

Leukocytes - metabolism

Details

Title: Subtitle: Biology of cerebral arteriovenous malformations with a focus on inflammation
Creators: Nikolaos Mouchtouris - Division of Neurovascular Surgery and Endovascular Neurosurgery, Department of Neurological Surgery, Thomas Jefferson University and Jefferson Hospital for Neuroscience, Philadelphia, Pennsylvania, USA
Pascal M Jabbour - Division of Neurovascular Surgery and Endovascular Neurosurgery, Department of Neurological Surgery, Thomas Jefferson University and Jefferson Hospital for Neuroscience, Philadelphia, Pennsylvania, USA
Robert M Starke - Department of Neurological Surgery, University of Virginia School of Medicine, Charlottesville, Virginia, USA
David M Hasan - Department of Neurosurgery, University of Iowa, Iowa City, Iowa, USA
Mario Zanaty - 1] Division of Neurovascular Surgery and Endovascular Neurosurgery, Department of Neurological Surgery, Thomas Jefferson University and Jefferson Hospital for Neuroscience, Philadelphia, Pennsylvania, USA Department of Neurosurgery, University of Iowa, Iowa City, Iowa, USA
Thana Theofanis - Division of Neurovascular Surgery and Endovascular Neurosurgery, Department of Neurological Surgery, Thomas Jefferson University and Jefferson Hospital for Neuroscience, Philadelphia, Pennsylvania, USA
Dale Ding - Department of Neurological Surgery, University of Virginia School of Medicine, Charlottesville, Virginia, USA
Stavropoula I Tjoumakaris - Division of Neurovascular Surgery and Endovascular Neurosurgery, Department of Neurological Surgery, Thomas Jefferson University and Jefferson Hospital for Neuroscience, Philadelphia, Pennsylvania, USA
Aaron S Dumont - Department of Neurological Surgery, Tulane University School of Medicine, New Orleans, Louisiana, USA
George M Ghobrial - Division of Neurovascular Surgery and Endovascular Neurosurgery, Department of Neurological Surgery, Thomas Jefferson University and Jefferson Hospital for Neuroscience, Philadelphia, Pennsylvania, USA
David Kung - Division of Neurovascular Surgery and Endovascular Neurosurgery, Department of Neurological Surgery, Thomas Jefferson University and Jefferson Hospital for Neuroscience, Philadelphia, Pennsylvania, USA
Robert H Rosenwasser - Division of Neurovascular Surgery and Endovascular Neurosurgery, Department of Neurological Surgery, Thomas Jefferson University and Jefferson Hospital for Neuroscience, Philadelphia, Pennsylvania, USA
Nohra Chalouhi - Division of Neurovascular Surgery and Endovascular Neurosurgery, Department of Neurological Surgery, Thomas Jefferson University and Jefferson Hospital for Neuroscience, Philadelphia, Pennsylvania, USA
Resource Type: Journal article
Publication Details: Journal of cerebral blood flow and metabolism, Vol.35(2), pp.167-175
DOI: 10.1038/jcbfm.2014.179
PMID: 25407267
PMCID: PMC4426734
NLM abbreviation: J Cereb Blood Flow Metab
ISSN: 0271-678X
eISSN: 1559-7016
Publisher: United States
Language: English
Date published: 02/2015
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Iowa Neuroscience Institute; Neurosurgery; Otolaryngology
Record Identifier: 9984040020502771

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