(Stroke. 2001;32:1036.)
© 2001 American Heart Association, Inc.
Original Contributions |
Molecular Anatomy of an Intracranial Aneurysm
Coordinated Expression of Genes Involved in Wound Healing and Tissue Remodeling
From the Department of Human Genetics, Graduate School of Public Health (D.G.P., E.H-O., R.E.F.), Department of Hematology/Oncology, School of Medicine (A.B.), and Department of Neurosurgery, School of Medicine (A.B.K., H.Y.), University of Pittsburgh (Pa).
Correspondence to David G. Peters, PhD, Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261. E-mail dpeters{at}helix.hgen.pitt.edu
Background and Purpose—Approximately 6% of human beings harbor an unruptured intracranial aneurysm. Each year in the United States, >30 000 people suffer a ruptured intracranial aneurysm, resulting in subarachnoid hemorrhage. Despite the high incidence and catastrophic consequences of a ruptured intracranial aneurysm and the fact that there is considerable evidence that predisposition to intracranial aneurysm has a strong genetic component, very little is understood with regard to the pathology and pathogenesis of this disease.
Methods—To begin characterizing the molecular pathology of intracranial aneurysm, we used a global gene expression analysis approach (SAGE-Lite) in combination with a novel data-mining approach to perform a high-resolution transcript analysis of a single intracranial aneurysm, obtained from a 3-year-old girl.
Results—SAGE-Lite provides a detailed molecular snapshot of a single intracranial aneurysm. These data suggest that, at least in this specific case, aneurysmal dilation results in a highly dynamic cellular environment in which extensive wound healing and tissue/extracellular matrix remodeling are taking place. Specifically, we observed significant overexpression of genes encoding extracellular matrix components (eg, COL3A1, COL1A1, COL1A2, COL6A1, COL6A2, elastin) and genes involved in extracellular matrix turnover (TIMP-3, OSF-2), cell adhesion and antiadhesion (SPARC, hevin), cytokinesis (PNUTL2), and cell migration (tetraspanin-5).
Conclusions—Although these are preliminary data, representing analysis of only one individual, we present a unique first insight into the molecular basis of aneurysmal disease and define numerous candidate markers for future biochemical, physiological, and genetic studies of intracranial aneurysm. Products of these genes will be the focus of future studies in wider sample sets.
Key Words: cerebral aneurysm • gene expression • stroke, hemorrhagic
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