Evidence map›Paper›PMID 26738788›Full record

ArticleJournal of the American Heart Association2016

Overexpression of Nitric Oxide Synthase Restores Circulating Angiogenic Cell Function in Patients With Coronary Artery Disease: Implications for Autologous Cell Therapy for Myocardial Infarction.

Qiumei Chen, Monika Varga, Xiaoyin Wang, Daniel J Haddad, Songtao An, Lejla Medzikovic, Ronak Derakhshandeh, Dmitry S Kostyushev, Yan Zhang, Brian T Clifford and 11 more

Open access · goldAbstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of the American Heart Association, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.2field-weighted citation impact, top 20% 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

7 citing papers in PubMed, 14 citations in OpenAlex.

  1. Novel prognostic impact and cell specific role of endocan in patients with coronary artery disease.Clinical research in cardiology : official journal of the German Cardiac Society · 2025
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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

21 authors at 4 institutions in 2 countries.

Qiumei ChenCardiovascular Research Institute, University of California, San Francisco, San Francisco, CA (Q.C., M.V., X.W., D.J.H., S.A., B.T.C., O.M.D., J.R.F., Y.Y., M.L.S.).
Monika VargaCardiovascular Research Institute, University of California, San Francisco, San Francisco, CA (Q.C., M.V., X.W., D.J.H., S.A., B.T.C., O.M.D., J.R.F., Y.Y., M.L.S.).
Xiaoyin WangCardiovascular Research Institute, University of California, San Francisco, San Francisco, CA (Q.C., M.V., X.W., D.J.H., S.A., B.T.C., O.M.D., J.R.F., Y.Y., M.L.S.).
Daniel J HaddadCardiovascular Research Institute, University of California, San Francisco, San Francisco, CA (Q.C., M.V., X.W., D.J.H., S.A., B.T.C., O.M.D., J.R.F., Y.Y., M.L.S.).
Songtao AnCardiovascular Research Institute, University of California, San Francisco, San Francisco, CA (Q.C., M.V., X.W., D.J.H., S.A., B.T.C., O.M.D., J.R.F., Y.Y., M.L.S.).
Lejla MedzikovicDivision of Cardiology, University of California, San Francisco, San Francisco, CA (L.M., R.D., D.S.K., Y.Z., E.L., C.H., Y.Y., M.L.S.).
Ronak DerakhshandehDivision of Cardiology, University of California, San Francisco, San Francisco, CA (L.M., R.D., D.S.K., Y.Z., E.L., C.H., Y.Y., M.L.S.).
Dmitry S KostyushevDivision of Cardiology, University of California, San Francisco, San Francisco, CA (L.M., R.D., D.S.K., Y.Z., E.L., C.H., Y.Y., M.L.S.).
Yan ZhangDivision of Cardiology, University of California, San Francisco, San Francisco, CA (L.M., R.D., D.S.K., Y.Z., E.L., C.H., Y.Y., M.L.S.).
Brian T CliffordCardiovascular Research Institute, University of California, San Francisco, San Francisco, CA (Q.C., M.V., X.W., D.J.H., S.A., B.T.C., O.M.D., J.R.F., Y.Y., M.L.S.).
Emmy LuuDivision of Cardiology, University of California, San Francisco, San Francisco, CA (L.M., R.D., D.S.K., Y.Z., E.L., C.H., Y.Y., M.L.S.).
Olivia M DanforthCardiovascular Research Institute, University of California, San Francisco, San Francisco, CA (Q.C., M.V., X.W., D.J.H., S.A., B.T.C., O.M.D., J.R.F., Y.Y., M.L.S.).
Ruslan RafikovDepartment of Medicine, University of Arizona, Tucson, AZ (R.R., S.M.B.).
Wenhui GongDepartment of Pediatrics, University of California, San Francisco, San Francisco, CA (W.G., J.R.F.).
Stephen M BlackDepartment of Medicine, University of Arizona, Tucson, AZ (R.R., S.M.B.).
Sergey V SuchkovI.M. Sechenov The First Moscow State Medical University, Moscow, Russia (S.V.S.).
Jeffrey R FinemanCardiovascular Research Institute, University of California, San Francisco, San Francisco, CA (Q.C., M.V., X.W., D.J.H., S.A., B.T.C., O.M.D., J.R.F., Y.Y., M.L.S.) Department of Pediatrics, University of California, San Francisco, San Francisco, CA (W.G., J.R.F.).
Christian HeissDivision of Cardiology, University of California, San Francisco, San Francisco, CA (L.M., R.D., D.S.K., Y.Z., E.L., C.H., Y.Y., M.L.S.).
Kirstin AschbacherDepartment of Psychiatry, University of California, San Francisco, San Francisco, CA (K.A.).
Yerem YeghiazariansCardiovascular Research Institute, University of California, San Francisco, San Francisco, CA (Q.C., M.V., X.W., D.J.H., S.A., B.T.C., O.M.D., J.R.F., Y.Y., M.L.S.) Division of Cardiology, University of California, San Francisco, San Francisco, CA (L.M., R.D., D.S.K., Y.Z., E.L., C.H., Y.Y., M.L.S.) Eli & Edythe Broad Institute of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA (Y.Y., M.L.S.).
Matthew L SpringerCardiovascular Research Institute, University of California, San Francisco, San Francisco, CA (Q.C., M.V., X.W., D.J.H., S.A., B.T.C., O.M.D., J.R.F., Y.Y., M.L.S.) Division of Cardiology, University of California, San Francisco, San Francisco, CA (L.M., R.D., D.S.K., Y.Z., E.L., C.H., Y.Y., M.L.S.) Eli & Edythe Broad Institute of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA (Y.Y., M.L.S.).
University of California, San Francisco · USBroad Center · USUniversity of Arizona · USSechenov University · RU

Funding

Therapeutic Mechanisms of RhoA Inhibition In Acute Lung InjuryP01HL101902 · NHLBI · AUGUSTA UNIVERSITY · PI BLACK, STEPHEN M · 2011 to 2016
$11.2M
PERINATAL REGULATION OF THE ENDOTHELIAL NOS GENER01HL060190 · NHLBI · UNIVERSITY OF MONTANA · PI Stephen M Black · 1998 to 2026
$7.1M
The Role of Nitric Oxide Synthase in Circulating Progenitor Cell FunctionR01HL086917 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SPRINGER, MATTHEW LAWRENCE · 2007 to 2011
$2.1M
Closed-Chest Cell Injections into Mouse Myocardium Targeted by UltrasoundR03EB005802 · NIBIB · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SPRINGER, MATTHEW LAWRENCE · 2005 to 2006
$150k
NHLBI NIH HHS P01 HL0101902NHLBI NIH HHS P01 HL101902NHLBI NIH HHS R01 HL060190NHLBI NIH HHS R01 HL086917NIBIB NIH HHS R03 EB005802
6 · The paper itself

Abstract

backgroundCirculating angiogenic cells (CACs) are peripheral blood cells whose functional capacity inversely correlates with cardiovascular risk and that have therapeutic benefits in animal models of cardiovascular disease. However, donor age and disease state influence the efficacy of autologous cell therapy. We sought to determine whether age or coronary artery disease (CAD) impairs the therapeutic potential of CACs for myocardial infarction (MI) and whether the use of ex vivo gene therapy to overexpress endothelial nitric oxide (NO) synthase (eNOS) overcomes these defects. METHODS AND

resultsWe recruited 40 volunteers varying by sex, age (< or ≥45 years), and CAD and subjected their CACs to well-established functional tests. Age and CAD were associated with reduced CAC intrinsic migration (but not specific response to vascular endothelial growth factor, adherence of CACs to endothelial tubes, eNOS mRNA and protein levels, and NO production. To determine how CAC function influences therapeutic potential, we injected the 2 most functional and the 2 least functional CAC isolates into mouse hearts post MI. The high-function isolates substantially improved cardiac function, whereas the low-function isolates led to cardiac function only slightly better than vehicle control. Transduction of the worst isolate with eNOS cDNA adenovirus increased NO production, migration, and cardiac function of post-MI mice implanted with the CACs. Transduction of the best isolate with eNOS small interfering RNA adenovirus reduced all of these capabilities.

conclusionsAge and CAD impair multiple functions of CACs and limit therapeutic potential for the treatment of MI. eNOS gene therapy in CACs from older donors or those with CAD has the potential to improve autologous cell therapy outcomes.

Indexed as

Neovascularization, PhysiologicAdultAgedAnimalsCase-Control StudiesCell MovementCells, CulturedCoculture TechniquesCoronary Artery DiseaseDisease Models, AnimalEndothelial Progenitor CellsFemaleHumansMaleMice, SCIDMiddle AgedNitric OxideNitric Oxide Synthase Type IIINOS3 protein, humancirculating angiogenic cellsendothelial progenitor cellsgene therapymyocardial infarctionnitric oxide synthase

Identifiers

PMID26738788
PMCPMC4859354
OpenAlexW2290711266

What OpenQuestion holds

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Registered trials

None linked

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.