title: Biology of cerebral arteriovenous malformations with a focus on inflammation.
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.
authors.affiliation: Division of Neurovascular Surgery and Endovascular Neurosurgery, Department of Neurological Surgery, Thomas Jefferson University and Jefferson Hospital for Neuroscience, Philadelphia, Pennsylvania, USA.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Mouchtouris
authors.affiliation: Division of Neurovascular Surgery and Endovascular Neurosurgery, Department of Neurological Surgery, Thomas Jefferson University and Jefferson Hospital for Neuroscience, Philadelphia, Pennsylvania, USA.
authors.forename: Pascal M
authors.initials: PM
authors.lastname: Jabbour
authors.affiliation: Department of Neurological Surgery, University of Virginia School of Medicine, Charlottesville, Virginia, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Starke
authors.affiliation: Department of Neurosurgery, University of Iowa, Iowa City, Iowa, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Hasan
authors.affiliation: 1] Division of Neurovascular Surgery and Endovascular Neurosurgery, Department of Neurological Surgery, Thomas Jefferson University and Jefferson Hospital for Neuroscience, Philadelphia, Pennsylvania, USA [2] Department of Neurosurgery, University of Iowa, Iowa City, Iowa, USA.
authors.forename: Mario
authors.initials: M
authors.lastname: Zanaty
authors.affiliation: Division of Neurovascular Surgery and Endovascular Neurosurgery, Department of Neurological Surgery, Thomas Jefferson University and Jefferson Hospital for Neuroscience, Philadelphia, Pennsylvania, USA.
authors.forename: Thana
authors.initials: T
authors.lastname: Theofanis
authors.affiliation: Department of Neurological Surgery, University of Virginia School of Medicine, Charlottesville, Virginia, USA.
authors.forename: Dale
authors.initials: D
authors.lastname: Ding
authors.affiliation: Division of Neurovascular Surgery and Endovascular Neurosurgery, Department of Neurological Surgery, Thomas Jefferson University and Jefferson Hospital for Neuroscience, Philadelphia, Pennsylvania, USA.
authors.forename: Stavropoula I
authors.initials: SI
authors.lastname: Tjoumakaris
authors.affiliation: Department of Neurological Surgery, Tulane University School of Medicine, New Orleans, Louisiana, USA.
authors.forename: Aaron S
authors.initials: AS
authors.lastname: Dumont
authors.affiliation: Division of Neurovascular Surgery and Endovascular Neurosurgery, Department of Neurological Surgery, Thomas Jefferson University and Jefferson Hospital for Neuroscience, Philadelphia, Pennsylvania, USA.
authors.forename: George M
authors.initials: GM
authors.lastname: Ghobrial
authors.affiliation: Division of Neurovascular Surgery and Endovascular Neurosurgery, Department of Neurological Surgery, Thomas Jefferson University and Jefferson Hospital for Neuroscience, Philadelphia, Pennsylvania, USA.
authors.forename: David
authors.initials: D
authors.lastname: Kung
authors.affiliation: Division of Neurovascular Surgery and Endovascular Neurosurgery, Department of Neurological Surgery, Thomas Jefferson University and Jefferson Hospital for Neuroscience, Philadelphia, Pennsylvania, USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Rosenwasser
authors.affiliation: Division of Neurovascular Surgery and Endovascular Neurosurgery, Department of Neurological Surgery, Thomas Jefferson University and Jefferson Hospital for Neuroscience, Philadelphia, Pennsylvania, USA.
authors.forename: Nohra
authors.initials: N
authors.lastname: Chalouhi
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002538:Intracranial Arteriovenous Malformations / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology*; D007962:Leukocytes / Q000378:metabolism / Q000473:pathology; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D015815:Cell Adhesion Molecules; D051880:Receptors, Notch; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9