Abstract 111: A Novel Role for Endogenous HGF in the Pathogenesis of Intracranial Aneurysms

• Published in: Stroke (1970) 2015-02, Vol.46 (suppl_1)
• Main Authors: Chalouhi, Nohra, Peña-Silva, Ricardo, Points, Lauren, Mitchell, Ian, Pierce, Gary, Faraci, Frank, Heistad, Donald, Ballas, Zuhair, Hasan, David
• Format: Article
• Language: English
• ISSN: 0039-2499; 1524-4628
• DOI: 10.1161/str.46.suppl_1.111

Abstract only Background and Purpose: Inflammation plays a key role in formation and rupture of intracranial aneurysms. Because hepatocyte growth factor (HGF) modulates vascular inflammation, we sought to assess the role of endogenous HGF in the pathogenesis of intracranial aneurysms. Methods: Circulating HGF concentrations in blood samples drawn from the lumen of human intracranial aneurysms or femoral arteries were compared in 16 patients. Intracranial aneurysm and superficial temporal artery tissue samples from patients undergoing clipping (n=10) were immunostained with antibodies to HGF and its receptor c-Met. Intracranial aneurysms were induced in mice treated with PF-04217903 (a c-Met antagonist) or vehicle. Expression of inflammatory molecules was also measured in cultured endothelial, smooth muscle cells and monocytes treated with LPS in presence or absence of HGF and PF-04217903. Results: HGF concentrations were significantly higher in blood collected from human intracranial aneurysm (1076 ± 656 pg/ml) than in femoral arteries (196 ± 436 pg/ml, p0.05), but significantly increased the prevalence of subarachnoid hemorrhage and decreased survival in mice (P