Abstract 111: A Novel Role for Endogenous HGF in the Pathogenesis of Intracranial Aneurysms
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<0.05). HGF attenuated expression of markers of inflammation in human aortic endothelial cells (P<0.05), but not in human aortic smooth muscle cells or monocytes.
Conclusion: Plasma HGF concentrations are higher in intracranial aneurysms. HGF and c-Met are expressed in intracranial aneurysms. HGF signaling through c-Met may decrease inflammation in endothelium and protect from intracranial aneurysm rupture. The findings of this study may have significant therapeutic implications for prevention of intracranial aneurysm formation and rupture.
Author Disclosures: N. Chalouhi: None. R. Peña-Silva: None. L. Points: None. I. Mitchell: None. G. Pierce: None. F. Faraci: None. D. Heistad: None. Z. Ballas: None. D. Hasan: None.
- © 2015 by American Heart Association, Inc.