Novel role for endogenous hepatocyte growth factor in the pathogenesis of intracranial aneurysms

Ricardo A Peña-Silva; Nohra Chalouhi; Lauren Wegman-Points; Muhammad Ali; Ian Mitchell; Gary L Pierce; Yi Chu; Zuhair K Ballas; Donald Heistad; David Hasan

doi:10.1161/HYPERTENSIONAHA.114.04681

Back

Novel role for endogenous hepatocyte growth factor in the pathogenesis of intracranial aneurysms

Journal article

Open access

Peer reviewed

Novel role for endogenous hepatocyte growth factor in the pathogenesis of intracranial aneurysms

Ricardo A Peña-Silva, Nohra Chalouhi, Lauren Wegman-Points, Muhammad Ali, Ian Mitchell, Gary L Pierce, Yi Chu, Zuhair K Ballas, Donald Heistad and David Hasan

Hypertension (Dallas, Tex. 1979), Vol.65(3), pp.587-593

03/2015

DOI: 10.1161/HYPERTENSIONAHA.114.04681

PMCID: PMC4326566

PMID: 25510828

Files and links (1)

url

https://doi.org/10.1161/HYPERTENSIONAHA.114.04681View

Published (Version of record) Open Access

Abstract

Inflammation plays a key role in formation and rupture of intracranial aneurysms. Because hepatocyte growth factor (HGF) protects against vascular inflammation, we sought to assess the role of endogenous HGF in the pathogenesis of intracranial aneurysms. Circulating HGF concentrations in blood samples drawn from the lumen of human intracranial aneurysms or femoral arteries were compared in 16 patients. Tissue from superficial temporal arteries and ruptured or unruptured intracranial aneurysms collected 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 human endothelial, smooth muscle cells and monocytes treated with lipopolysaccharides in presence or absence of HGF and PF-04217903. We found that HGF concentrations were significantly higher in blood collected from human intracranial aneurysms (1076±656 pg/mL) than in femoral arteries (196±436 pg/mL; P<0.001). HGF and c-Met were detected by immunostaining in superficial temporal arteries and in both ruptured and unruptured human intracranial aneurysms. A c-Met antagonist did not alter the formation of intracranial aneurysms (P>0.05), but significantly increased the prevalence of subarachnoid hemorrhage and decreased survival in mice (P<0.05). HGF attenuated expression of vascular cell adhesion molecule-1 (P<0.05) and E-Selectin (P<0.05) in human aortic endothelial cells. In conclusion, plasma HGF concentrations are elevated in intracranial aneurysms. HGF and c-Met are expressed in superficial temporal arteries and in intracranial aneurysms. HGF signaling through c-Met may decrease inflammation in endothelial cells and protect against intracranial aneurysm rupture.

Proto-Oncogene Proteins c-met - metabolism

Triazoles - adverse effects

Muscle, Smooth, Vascular - metabolism

Humans

Middle Aged

Endothelium, Vascular - drug effects

Male

Aneurysm, Ruptured - etiology

Hepatocyte Growth Factor - pharmacology

Aneurysm, Ruptured - physiopathology

Hepatocyte Growth Factor - physiology

Adult

Female

Disease Models, Animal

Muscle, Smooth, Vascular - drug effects

Proto-Oncogene Proteins c-met - antagonists & inhibitors

Mice, Inbred C57BL

Cells, Cultured

Proto-Oncogene Proteins c-met - drug effects

E-Selectin - metabolism

Intracranial Aneurysm - metabolism

Triazoles - pharmacology

Intracranial Aneurysm - etiology

Muscle, Smooth, Vascular - pathology

Animals

Hepatocyte Growth Factor - blood

Endothelium, Vascular - metabolism

Aneurysm, Ruptured - metabolism

Pyrazines - adverse effects

Endothelium, Vascular - pathology

Signal Transduction - physiology

Aged

Mice

Intracranial Aneurysm - physiopathology

Pyrazines - pharmacology

Vascular Cell Adhesion Molecule-1 - metabolism

Details

Title: Subtitle: Novel role for endogenous hepatocyte growth factor in the pathogenesis of intracranial aneurysms
Creators: Ricardo A Peña-Silva - From the Departments of Pharmacology and Neurosurgery, Medical School, Universidad de los Andes, Bogotá, Colombia (R.A.P.-S.); Department of Neurosurgery, Thomas Jefferson University School of Medicine, Philadelphia, PA (N.C.); Department of Health and Human Physiology, University of Iowa, Iowa City (L.W.-P., G.L.P.); Departments of Neurosurgery (M.A., I.M., Y.C., D. Hasan) and Medicine (Y.C., Z.K.B., D. Heistad), University of Iowa Carver College of Medicine, Iowa City; and Department of Medicine, VA Medical Center, Iowa City, IA (Z.K.B.)
Nohra Chalouhi - From the Departments of Pharmacology and Neurosurgery, Medical School, Universidad de los Andes, Bogotá, Colombia (R.A.P.-S.); Department of Neurosurgery, Thomas Jefferson University School of Medicine, Philadelphia, PA (N.C.); Department of Health and Human Physiology, University of Iowa, Iowa City (L.W.-P., G.L.P.); Departments of Neurosurgery (M.A., I.M., Y.C., D. Hasan) and Medicine (Y.C., Z.K.B., D. Heistad), University of Iowa Carver College of Medicine, Iowa City; and Department of Medicine, VA Medical Center, Iowa City, IA (Z.K.B.)
Lauren Wegman-Points - From the Departments of Pharmacology and Neurosurgery, Medical School, Universidad de los Andes, Bogotá, Colombia (R.A.P.-S.); Department of Neurosurgery, Thomas Jefferson University School of Medicine, Philadelphia, PA (N.C.); Department of Health and Human Physiology, University of Iowa, Iowa City (L.W.-P., G.L.P.); Departments of Neurosurgery (M.A., I.M., Y.C., D. Hasan) and Medicine (Y.C., Z.K.B., D. Heistad), University of Iowa Carver College of Medicine, Iowa City; and Department of Medicine, VA Medical Center, Iowa City, IA (Z.K.B.)
Muhammad Ali - From the Departments of Pharmacology and Neurosurgery, Medical School, Universidad de los Andes, Bogotá, Colombia (R.A.P.-S.); Department of Neurosurgery, Thomas Jefferson University School of Medicine, Philadelphia, PA (N.C.); Department of Health and Human Physiology, University of Iowa, Iowa City (L.W.-P., G.L.P.); Departments of Neurosurgery (M.A., I.M., Y.C., D. Hasan) and Medicine (Y.C., Z.K.B., D. Heistad), University of Iowa Carver College of Medicine, Iowa City; and Department of Medicine, VA Medical Center, Iowa City, IA (Z.K.B.)
Ian Mitchell - From the Departments of Pharmacology and Neurosurgery, Medical School, Universidad de los Andes, Bogotá, Colombia (R.A.P.-S.); Department of Neurosurgery, Thomas Jefferson University School of Medicine, Philadelphia, PA (N.C.); Department of Health and Human Physiology, University of Iowa, Iowa City (L.W.-P., G.L.P.); Departments of Neurosurgery (M.A., I.M., Y.C., D. Hasan) and Medicine (Y.C., Z.K.B., D. Heistad), University of Iowa Carver College of Medicine, Iowa City; and Department of Medicine, VA Medical Center, Iowa City, IA (Z.K.B.)
Gary L Pierce - From the Departments of Pharmacology and Neurosurgery, Medical School, Universidad de los Andes, Bogotá, Colombia (R.A.P.-S.); Department of Neurosurgery, Thomas Jefferson University School of Medicine, Philadelphia, PA (N.C.); Department of Health and Human Physiology, University of Iowa, Iowa City (L.W.-P., G.L.P.); Departments of Neurosurgery (M.A., I.M., Y.C., D. Hasan) and Medicine (Y.C., Z.K.B., D. Heistad), University of Iowa Carver College of Medicine, Iowa City; and Department of Medicine, VA Medical Center, Iowa City, IA (Z.K.B.)
Yi Chu - From the Departments of Pharmacology and Neurosurgery, Medical School, Universidad de los Andes, Bogotá, Colombia (R.A.P.-S.); Department of Neurosurgery, Thomas Jefferson University School of Medicine, Philadelphia, PA (N.C.); Department of Health and Human Physiology, University of Iowa, Iowa City (L.W.-P., G.L.P.); Departments of Neurosurgery (M.A., I.M., Y.C., D. Hasan) and Medicine (Y.C., Z.K.B., D. Heistad), University of Iowa Carver College of Medicine, Iowa City; and Department of Medicine, VA Medical Center, Iowa City, IA (Z.K.B.)
Zuhair K Ballas - From the Departments of Pharmacology and Neurosurgery, Medical School, Universidad de los Andes, Bogotá, Colombia (R.A.P.-S.); Department of Neurosurgery, Thomas Jefferson University School of Medicine, Philadelphia, PA (N.C.); Department of Health and Human Physiology, University of Iowa, Iowa City (L.W.-P., G.L.P.); Departments of Neurosurgery (M.A., I.M., Y.C., D. Hasan) and Medicine (Y.C., Z.K.B., D. Heistad), University of Iowa Carver College of Medicine, Iowa City; and Department of Medicine, VA Medical Center, Iowa City, IA (Z.K.B.)
Donald Heistad - From the Departments of Pharmacology and Neurosurgery, Medical School, Universidad de los Andes, Bogotá, Colombia (R.A.P.-S.); Department of Neurosurgery, Thomas Jefferson University School of Medicine, Philadelphia, PA (N.C.); Department of Health and Human Physiology, University of Iowa, Iowa City (L.W.-P., G.L.P.); Departments of Neurosurgery (M.A., I.M., Y.C., D. Hasan) and Medicine (Y.C., Z.K.B., D. Heistad), University of Iowa Carver College of Medicine, Iowa City; and Department of Medicine, VA Medical Center, Iowa City, IA (Z.K.B.)
David Hasan - From the Departments of Pharmacology and Neurosurgery, Medical School, Universidad de los Andes, Bogotá, Colombia (R.A.P.-S.); Department of Neurosurgery, Thomas Jefferson University School of Medicine, Philadelphia, PA (N.C.); Department of Health and Human Physiology, University of Iowa, Iowa City (L.W.-P., G.L.P.); Departments of Neurosurgery (M.A., I.M., Y.C., D. Hasan) and Medicine (Y.C., Z.K.B., D. Heistad), University of Iowa Carver College of Medicine, Iowa City; and Department of Medicine, VA Medical Center, Iowa City, IA (Z.K.B.). david-hasan@uiowa.edu
Resource Type: Journal article
Publication Details: Hypertension (Dallas, Tex. 1979), Vol.65(3), pp.587-593
Publisher: United States
DOI: 10.1161/HYPERTENSIONAHA.114.04681
PMID: 25510828
PMCID: PMC4326566
ISSN: 0194-911X
eISSN: 1524-4563
Grant note: P01 HL014388 / NHLBI NIH HHS K08 NS082363 / NINDS NIH HHS R03 NS079227 / NINDS NIH HHS K08NS082363 / NINDS NIH HHS
Language: English
Date published: 03/2015
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Cardiovascular Medicine; Neuroscience and Pharmacology; Immunology; Neurosurgery; Otolaryngology; Health and Human Physiology; Internal Medicine
Record Identifier: 9984040339302771

Metrics

17 Record Views

25 Times Cited - Web of Science

See more details