Evidence map›Paper›PMID 27354285›Full record

ArticleCirculation2016

Elevated Angiopoietin-2 Level in Patients With Continuous-Flow Left Ventricular Assist Devices Leads to Altered Angiogenesis and Is Associated With Higher Nonsurgical Bleeding.

Corey E Tabit, Phetcharat Chen, Gene H Kim, Savitri E Fedson, Gabriel Sayer, Mitchell J Coplan, Valluvan Jeevanandam, Nir Uriel, James K Liao

Open access · bronzeAbstract read
In one paragraph

Article in Circulation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed, 1 pooled it
13.9field-weighted citation impact, top 1% 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

55 citing papers in PubMed, 1 synthesis or guideline pooled it, 148 citations in OpenAlex.

  1. Blood stream infection is associated with cerebrovascular accident in patients with left ventricular assist device: a systematic review and meta-analysis.Journal of artificial organs : the official journal of the Japanese Society for Artificial Organs · 2018
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  5. Impact and outcomes after desensitization therapy in highly sensitized heart transplant candidates.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2026
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  17. Impact of the elevated angiopoietin-2 levels during Impella support on the short-term prognosis.Journal of artificial organs : the official journal of the Japanese Society for Artificial Organs · 2023
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 1 institution in 1 country.

Corey E TabitFrom the Department of Medicine, Section of Cardiology (C.E.T., P.C., G.H.K., G.S., M.J.C., N.U., J.K.L.) and Department of Surgery, Section of Cardiac and Thoracic Surgery (V.T.), University of Chicago, IL; and Section of Cardiology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX (S.E.F.).
Phetcharat ChenFrom the Department of Medicine, Section of Cardiology (C.E.T., P.C., G.H.K., G.S., M.J.C., N.U., J.K.L.) and Department of Surgery, Section of Cardiac and Thoracic Surgery (V.T.), University of Chicago, IL; and Section of Cardiology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX (S.E.F.).
Gene H KimFrom the Department of Medicine, Section of Cardiology (C.E.T., P.C., G.H.K., G.S., M.J.C., N.U., J.K.L.) and Department of Surgery, Section of Cardiac and Thoracic Surgery (V.T.), University of Chicago, IL; and Section of Cardiology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX (S.E.F.).
Savitri E FedsonFrom the Department of Medicine, Section of Cardiology (C.E.T., P.C., G.H.K., G.S., M.J.C., N.U., J.K.L.) and Department of Surgery, Section of Cardiac and Thoracic Surgery (V.T.), University of Chicago, IL; and Section of Cardiology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX (S.E.F.).
Gabriel SayerFrom the Department of Medicine, Section of Cardiology (C.E.T., P.C., G.H.K., G.S., M.J.C., N.U., J.K.L.) and Department of Surgery, Section of Cardiac and Thoracic Surgery (V.T.), University of Chicago, IL; and Section of Cardiology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX (S.E.F.).
Mitchell J CoplanFrom the Department of Medicine, Section of Cardiology (C.E.T., P.C., G.H.K., G.S., M.J.C., N.U., J.K.L.) and Department of Surgery, Section of Cardiac and Thoracic Surgery (V.T.), University of Chicago, IL; and Section of Cardiology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX (S.E.F.).
Valluvan JeevanandamFrom the Department of Medicine, Section of Cardiology (C.E.T., P.C., G.H.K., G.S., M.J.C., N.U., J.K.L.) and Department of Surgery, Section of Cardiac and Thoracic Surgery (V.T.), University of Chicago, IL; and Section of Cardiology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX (S.E.F.).
Nir UrielFrom the Department of Medicine, Section of Cardiology (C.E.T., P.C., G.H.K., G.S., M.J.C., N.U., J.K.L.) and Department of Surgery, Section of Cardiac and Thoracic Surgery (V.T.), University of Chicago, IL; and Section of Cardiology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX (S.E.F.).
James K LiaoFrom the Department of Medicine, Section of Cardiology (C.E.T., P.C., G.H.K., G.S., M.J.C., N.U., J.K.L.) and Department of Surgery, Section of Cardiac and Thoracic Surgery (V.T.), University of Chicago, IL; and Section of Cardiology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX (S.E.F.). jliao@medicine.bsd.uchicago.edu.
Michael E. DeBakey VA Medical Center · US

Funding

Re-Engineering Translational Research at the University of ChicagoUL1TR000430 · NCATS · UNIVERSITY OF CHICAGO · PI SOLWAY, JULIAN · 2012 to 2016
$20.2M
LIPOPROTEINS EFFECTS ON G PROTEIN FUNCTIONR01HL052233 · NHLBI · UNIVERSITY OF CHICAGO · PI LIAO, JAMES KUANG-JAN · 1995 to 2016
$5.3M
Summer Program to Increase Heart, Lung, and Blood Biomedical ResearchR25HL096383 · NHLBI · UNIVERSITY OF CHICAGO · PI CHRISTOPHER O OLOPADE, William F Parker · 2009 to 2026
$2.1M
Novel Signaling Pathways in Ischemic StrokeR01NS070001 · NINDS · UNIVERSITY OF CHICAGO · PI LIAO, JAMES KUANG-JAN · 2010 to 2014
$1.8M
American Heart Association-American Stroke AssociationNCATS NIH HHS UL1 TR000430NHLBI NIH HHS R01 HL052233NHLBI NIH HHS R25 HL096383NINDS NIH HHS R01 NS070001
6 · The paper itself

Abstract

backgroundNonsurgical bleeding is the most common adverse event in patients with continuous-flow left ventricular assist devices (LVADs) and is caused by arteriovenous malformations. We hypothesized that deregulation of an angiogenic factor, angiopoietin-2 (Ang-2), in patients with LVADs leads to increased angiogenesis and higher nonsurgical bleeding.

methodsAng-2 and thrombin levels were measured by ELISA and Western blotting, respectively, in blood samples from 101 patients with heart failure, LVAD, or orthotopic heart transplantation. Ang-2 expression in endothelial biopsy was quantified by immunofluorescence. Angiogenesis was determined by in vitro tube formation from serum from each patient with or without Ang-2-blocking antibody. Ang-2 gene expression was measured by reverse transcription-polymerase chain reaction in endothelial cells incubated with plasma from each patient with or without the thrombin receptor blocker vorapaxar.

resultsCompared with patients with heart failure or those with orthotopic heart transplantation, serum levels and endothelial expression of Ang-2 were higher in LVAD patients (P=0.001 and P<0.001, respectively). This corresponded to an increased angiogenic potential of serum from patients with LVADs (P<0.001), which was normalized with Ang-2 blockade. Furthermore, plasma from LVAD patients contained higher amounts of thrombin (P=0.003), which was associated with activation of the contact coagulation system. Plasma from LVAD patients induced more Ang-2 gene expression in endothelial cells (P<0.001), which was reduced with thrombin receptor blockade (P=0.013). LVAD patients with Ang-2 levels above the mean (12.32 ng/mL) had more nonsurgical bleeding events compared with patients with Ang-2 levels below the mean (P=0.003).

conclusionsOur findings indicate that thrombin-induced Ang-2 expression in LVAD patients leads to increased angiogenesis in vitro and may be associated with higher nonsurgical bleeding events. Ang-2 therefore may contribute to arteriovenous malformation formation and subsequent bleeding in LVAD patients.

Indexed as

AgedAngiopoietin-2Arteriovenous MalformationsBiomarkersCross-Sectional StudiesEndothelial CellsFemaleHeart-Assist DevicesHemorrhageHumansHuman Umbilical Vein Endothelial CellsMaleMiddle AgedNeovascularization, PathologicThrombinAngiopoietin-2BiomarkersThrombinangiogenesisangiopoietin-2cardiac transplantLVADnonsurgical bleedingthrombin

Identifiers

PMID27354285
PMCPMC4942355
OpenAlexW2497397127

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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.