Skip to main content

Myeloperoxidase is increased in human cerebral aneurysms and increases formation and rupture of cerebral aneurysms in mice.

Publication ,  Journal Article
Chu, Y; Wilson, K; Gu, H; Wegman-Points, L; Dooley, SA; Pierce, GL; Cheng, G; Pena Silva, RA; Heistad, DD; Hasan, D
Published in: Stroke
June 2015

BACKGROUND AND PURPOSE: Cerebral aneurysm (CA) affects 3% of the population and is associated with hemodynamic stress and inflammation. Myeloperoxidase, a major oxidative enzyme associated with inflammation, is increased in patients with CA, but whether myeloperoxidase contributes to CA is not known. We tested the hypotheses that myeloperoxidase is increased within human CA and is critical for formation and rupture of CA in mice. METHODS: Blood was drawn from the lumen of CAs and femoral arteries of 25 patients who underwent endovascular coiling of CA, and plasma myeloperoxidase concentrations were measured with ELISA. Effects of endogenous myeloperoxidase on CA formation and rupture were studied in myeloperoxidase knockout mice and wild-type (WT) mice using an angiotensin II-elastase induction model of CA. In addition, effects of myeloperoxidase on inflammatory gene expression in endothelial cells were analyzed. RESULTS: Plasma concentrations of myeloperoxidase were 2.7-fold higher within CA than in femoral arterial blood in patients with CA. myeloperoxidase-positive cells were increased in aneurysm tissue compared with superficial temporal artery of patients with CA. Incidence of aneurysms and subarachnoid hemorrhage was significantly lower in myeloperoxidase knockout than in WT mice. In cerebral arteries, proinflammatory molecules, including tumor necrosis factor-α, cyclooxygenase-2 (COX2), chemokine (C-X-C motif) ligand 1 (CXCL1), chemokine (C motif) ligand (XCL1), matrix metalloproteinase (MMP) 8, cluster of differentiation 68 (CD68), and matrix metalloproteinase 13, and leukocytes were increased, and α-smooth muscle actin was decreased, in WT but not in myeloperoxidase knockout mice after induction of CA. Myeloperoxidase per se increased expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 in endothelial cells. CONCLUSIONS: These findings suggest that myeloperoxidase may contribute importantly to formation and rupture of CA.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Stroke

DOI

EISSN

1524-4628

Publication Date

June 2015

Volume

46

Issue

6

Start / End Page

1651 / 1656

Location

United States

Related Subject Headings

  • Vasoconstrictor Agents
  • Vascular Cell Adhesion Molecule-1
  • Peroxidase
  • Pancreatic Elastase
  • Neurology & Neurosurgery
  • Mice, Knockout
  • Mice
  • Male
  • Leukocyte Count
  • Intracranial Aneurysm
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Chu, Y., Wilson, K., Gu, H., Wegman-Points, L., Dooley, S. A., Pierce, G. L., … Hasan, D. (2015). Myeloperoxidase is increased in human cerebral aneurysms and increases formation and rupture of cerebral aneurysms in mice. Stroke, 46(6), 1651–1656. https://doi.org/10.1161/STROKEAHA.114.008589
Chu, Yi, Katina Wilson, He Gu, Lauren Wegman-Points, Sarah A. Dooley, Gary L. Pierce, Guangjie Cheng, Ricardo A. Pena Silva, Donald D. Heistad, and David Hasan. “Myeloperoxidase is increased in human cerebral aneurysms and increases formation and rupture of cerebral aneurysms in mice.Stroke 46, no. 6 (June 2015): 1651–56. https://doi.org/10.1161/STROKEAHA.114.008589.
Chu Y, Wilson K, Gu H, Wegman-Points L, Dooley SA, Pierce GL, et al. Myeloperoxidase is increased in human cerebral aneurysms and increases formation and rupture of cerebral aneurysms in mice. Stroke. 2015 Jun;46(6):1651–6.
Chu, Yi, et al. “Myeloperoxidase is increased in human cerebral aneurysms and increases formation and rupture of cerebral aneurysms in mice.Stroke, vol. 46, no. 6, June 2015, pp. 1651–56. Pubmed, doi:10.1161/STROKEAHA.114.008589.
Chu Y, Wilson K, Gu H, Wegman-Points L, Dooley SA, Pierce GL, Cheng G, Pena Silva RA, Heistad DD, Hasan D. Myeloperoxidase is increased in human cerebral aneurysms and increases formation and rupture of cerebral aneurysms in mice. Stroke. 2015 Jun;46(6):1651–1656.

Published In

Stroke

DOI

EISSN

1524-4628

Publication Date

June 2015

Volume

46

Issue

6

Start / End Page

1651 / 1656

Location

United States

Related Subject Headings

  • Vasoconstrictor Agents
  • Vascular Cell Adhesion Molecule-1
  • Peroxidase
  • Pancreatic Elastase
  • Neurology & Neurosurgery
  • Mice, Knockout
  • Mice
  • Male
  • Leukocyte Count
  • Intracranial Aneurysm