title: The role of vascular remodeling and inflammation in the pathogenesis of intracranial aneurysms.
abstract: While the mechanisms triggering pathogenesis of intracranial aneurysms have not been fully elucidated, different mechanisms have been proposed ranging from hemodynamic mechanisms to genetic predispositions. One mechanism that has been thoroughly explored is the physiological and pathological vascular remodeling that occurs in conjunction with inflammatory reactions resulting in the initiation and progression of these lesions. Both hemodynamic stimuli and vascular inflammation can trigger a series of biochemical reactions resulting in vascular smooth muscle cell apoptosis and migration causing thinned, dilated areas of the cerebral vasculature. In addition, an imbalance between extracellular matrix remodeling proteins, such as matrix metalloproteinases and their inhibitors, can result in accelerated degradation of the internal elastic lamina and the adventitial layers, further weakening the vessel. While these processes occur under normal physiological conditions, situations that alter their balance such as inflammation caused by cigarette smoking or cocaine usage or hypoxia induced under chronic hypertensive conditions can alter the delicate balance of these reactions potentiating pathological remodeling and aneurysm development. The present study represents a thorough literature review of the vascular remodeling and inflammatory components to aneurysmal pathogenesis.
authors.affiliation: Department of Neurological Surgery, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, AB-136, Boston, MA 02115, USA. Electronic address: DLP628@gmail.com.
authors.forename: David L
authors.initials: DL
authors.lastname: Penn
authors.affiliation: Department of Neurological Surgery, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Samantha R
authors.initials: SR
authors.lastname: Witte
authors.affiliation: Department of Neurological Surgery, University of Miami, Miami, FL, USA.
authors.forename: Ricardo J
authors.initials: RJ
authors.lastname: Komotar
authors.affiliation: Department of Neurological Surgery, New York-Presbyterian Hospital, Columbia University, New York, NY, USA.
authors.forename: E
authors.initials: E
authors.lastname: Sander Connolly
mesh_terms: D000818:Animals; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology*; D002532:Intracranial Aneurysm / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology*
keywords: Aneurysms; Inflammation; Matrix metalloproteinases; Vascular remodeling