Evidence map›Paper›PMID 25922506›Full record

Trial reportStroke2015

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

Yi Chu, Katina Wilson, He Gu, Lauren Wegman-Points, Sarah A Dooley, Gary L Pierce, Guangjie Cheng, Ricardo A Pena Silva, Donald D Heistad, David Hasan

Abstract readClinical Trial
In one paragraph

Trial report in Stroke, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 2 pooled it
3.8field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

32 citing papers in PubMed, 2 syntheses or guidelines pooled it, 80 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 1 institution in 1 country.

Yi ChuFrom the Departments of Neurosurgery (Y.C., K.W., H.G., S.A.D., D.H.), Internal Medicine (Y.C., K.W., D.D.H.), Anesthesiology (H.G.), and Health and Human Physiology (L.W.-P., G.L.P.), University of Iowa Carver College of Medicine; Department of Internal Medicine, University of Alabama School of Medicine, Birmingham (G.C.); and Departments of Pharmacology and Neurosurgery, Medical School, Universidad de los Andes, Bogota, Colombia (R.A.P.S.).
Katina WilsonFrom the Departments of Neurosurgery (Y.C., K.W., H.G., S.A.D., D.H.), Internal Medicine (Y.C., K.W., D.D.H.), Anesthesiology (H.G.), and Health and Human Physiology (L.W.-P., G.L.P.), University of Iowa Carver College of Medicine; Department of Internal Medicine, University of Alabama School of Medicine, Birmingham (G.C.); and Departments of Pharmacology and Neurosurgery, Medical School, Universidad de los Andes, Bogota, Colombia (R.A.P.S.).
He GuFrom the Departments of Neurosurgery (Y.C., K.W., H.G., S.A.D., D.H.), Internal Medicine (Y.C., K.W., D.D.H.), Anesthesiology (H.G.), and Health and Human Physiology (L.W.-P., G.L.P.), University of Iowa Carver College of Medicine; Department of Internal Medicine, University of Alabama School of Medicine, Birmingham (G.C.); and Departments of Pharmacology and Neurosurgery, Medical School, Universidad de los Andes, Bogota, Colombia (R.A.P.S.).
Lauren Wegman-PointsFrom the Departments of Neurosurgery (Y.C., K.W., H.G., S.A.D., D.H.), Internal Medicine (Y.C., K.W., D.D.H.), Anesthesiology (H.G.), and Health and Human Physiology (L.W.-P., G.L.P.), University of Iowa Carver College of Medicine; Department of Internal Medicine, University of Alabama School of Medicine, Birmingham (G.C.); and Departments of Pharmacology and Neurosurgery, Medical School, Universidad de los Andes, Bogota, Colombia (R.A.P.S.).
Sarah A DooleyFrom the Departments of Neurosurgery (Y.C., K.W., H.G., S.A.D., D.H.), Internal Medicine (Y.C., K.W., D.D.H.), Anesthesiology (H.G.), and Health and Human Physiology (L.W.-P., G.L.P.), University of Iowa Carver College of Medicine; Department of Internal Medicine, University of Alabama School of Medicine, Birmingham (G.C.); and Departments of Pharmacology and Neurosurgery, Medical School, Universidad de los Andes, Bogota, Colombia (R.A.P.S.).
Gary L PierceFrom the Departments of Neurosurgery (Y.C., K.W., H.G., S.A.D., D.H.), Internal Medicine (Y.C., K.W., D.D.H.), Anesthesiology (H.G.), and Health and Human Physiology (L.W.-P., G.L.P.), University of Iowa Carver College of Medicine; Department of Internal Medicine, University of Alabama School of Medicine, Birmingham (G.C.); and Departments of Pharmacology and Neurosurgery, Medical School, Universidad de los Andes, Bogota, Colombia (R.A.P.S.).
Guangjie ChengFrom the Departments of Neurosurgery (Y.C., K.W., H.G., S.A.D., D.H.), Internal Medicine (Y.C., K.W., D.D.H.), Anesthesiology (H.G.), and Health and Human Physiology (L.W.-P., G.L.P.), University of Iowa Carver College of Medicine; Department of Internal Medicine, University of Alabama School of Medicine, Birmingham (G.C.); and Departments of Pharmacology and Neurosurgery, Medical School, Universidad de los Andes, Bogota, Colombia (R.A.P.S.).
Ricardo A Pena SilvaFrom the Departments of Neurosurgery (Y.C., K.W., H.G., S.A.D., D.H.), Internal Medicine (Y.C., K.W., D.D.H.), Anesthesiology (H.G.), and Health and Human Physiology (L.W.-P., G.L.P.), University of Iowa Carver College of Medicine; Department of Internal Medicine, University of Alabama School of Medicine, Birmingham (G.C.); and Departments of Pharmacology and Neurosurgery, Medical School, Universidad de los Andes, Bogota, Colombia (R.A.P.S.).
Donald D HeistadFrom the Departments of Neurosurgery (Y.C., K.W., H.G., S.A.D., D.H.), Internal Medicine (Y.C., K.W., D.D.H.), Anesthesiology (H.G.), and Health and Human Physiology (L.W.-P., G.L.P.), University of Iowa Carver College of Medicine; Department of Internal Medicine, University of Alabama School of Medicine, Birmingham (G.C.); and Departments of Pharmacology and Neurosurgery, Medical School, Universidad de los Andes, Bogota, Colombia (R.A.P.S.).
David HasanFrom the Departments of Neurosurgery (Y.C., K.W., H.G., S.A.D., D.H.), Internal Medicine (Y.C., K.W., D.D.H.), Anesthesiology (H.G.), and Health and Human Physiology (L.W.-P., G.L.P.), University of Iowa Carver College of Medicine; Department of Internal Medicine, University of Alabama School of Medicine, Birmingham (G.C.); and Departments of Pharmacology and Neurosurgery, Medical School, Universidad de los Andes, Bogota, Colombia (R.A.P.S.). david-hasan@uiowa.edu.
University of Alabama · US

Funding

Vascular Protection During HypertensionP01HL062984 · NHLBI · UNIVERSITY OF IOWA · PI FARACI, FRANK M · 2000 to 2015
$22.2M
Mechanisms of Effect of Aspirin on Cerebral Aneurysms in MiceK08NS082363 · NINDS · UNIVERSITY OF IOWA · PI HASAN, DAVID M. · 2013 to 2017
$846k
NHLBI NIH HHS HL62984NHLBI NIH HHS P01 HL062984NINDS NIH HHS K08 NS082363NINDS NIH HHS NS082363
6 · The paper itself

Abstract

background and purposeCerebral 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.

methodsBlood 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.

resultsPlasma 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.

conclusionsThese findings suggest that myeloperoxidase may contribute importantly to formation and rupture of CA.

Indexed as

Aneurysm, RupturedAngiotensin IIAnimalsDisease Models, AnimalGene Expression RegulationHumansInflammation MediatorsIntercellular Adhesion Molecule-1Intracranial AneurysmLeukocyte CountMaleMiceMice, KnockoutPancreatic ElastasePeroxidaseVascular Cell Adhesion Molecule-1Angiotensin IIICAM1 protein, humanIcam1 protein, mouseInflammation MediatorsIntercellular Adhesion Molecule-1Pancreatic ElastasePeroxidaseVascular Cell Adhesion Molecule-1Vasoconstrictor Agentsinflammationintercellular adhesion molecule-1intracranial aneurysmneutrophilsperoxidase subarachnoid hemorrhagevascular cell adhesion molecule-1

Identifiers

PMID25922506
PMCPMC4418183
OpenAlexW2026235171

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.