Evidence map›Paper›PMID 26699654›Full record

ArticleCirculation research2016

Critical Role for Telomerase in the Mechanism of Flow-Mediated Dilation in the Human Microcirculation.

Andreas M Beyer, Julie K Freed, Matthew J Durand, Michael Riedel, Karima Ait-Aissa, Paula Green, Joseph C Hockenberry, R Garret Morgan, Anthony J Donato, Refael Peleg and 5 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed, 1 pooled it
6.4field-weighted citation impact, top 3% 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

66 citing papers in PubMed, 1 synthesis or guideline pooled it, 111 citations in OpenAlex.

  1. Telomere Biology and Thoracic Aortic Aneurysm.International journal of molecular sciences · 2017
    Pooled it
  2. Trial
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  7. Article
  8. Review
  9. Review
  10. Endothelial TERT drives microvascular phenotype associated with coronary artery disease.American journal of physiology. Heart and circulatory physiology · 2025
    Article
  11. Article
  12. A chronology of basic and clinical research in the coronary microcirculation.Journal of molecular and cellular cardiology · 2025
    Article
  13. Article
  14. Article
  15. Review
  16. Article
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6 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 3 institutions in 1 country.

Andreas M BeyerFrom the Department of Medicine, Cardiovascular Center (A.M.B., M.J.D., M.R., K.A.-A., J.C.H., D.D.G.), Department of Physiology (A.M.B., K.A.-A., D.D.G.), Department of Anesthesiology (J.K.F.), Department of Physical Medicine and Rehabilitation (M.J.D.), and Departments of Surgery, Cardiothoracic Surgery (M.G., C.K.R.), Medical College of Wisconsin, Milwaukee; Departments of Pharmacology and Physiology, New Jersey Medical School of Rutgers, Newark (P.G., J.H.S.); Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City (R.G.M., A.J.D.); and Shraga Segal Departments of Immunology and Microbiology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel (R.P., E.P.). abeyer@mcw.edu.
Julie K FreedFrom the Department of Medicine, Cardiovascular Center (A.M.B., M.J.D., M.R., K.A.-A., J.C.H., D.D.G.), Department of Physiology (A.M.B., K.A.-A., D.D.G.), Department of Anesthesiology (J.K.F.), Department of Physical Medicine and Rehabilitation (M.J.D.), and Departments of Surgery, Cardiothoracic Surgery (M.G., C.K.R.), Medical College of Wisconsin, Milwaukee; Departments of Pharmacology and Physiology, New Jersey Medical School of Rutgers, Newark (P.G., J.H.S.); Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City (R.G.M., A.J.D.); and Shraga Segal Departments of Immunology and Microbiology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel (R.P., E.P.).
Matthew J DurandFrom the Department of Medicine, Cardiovascular Center (A.M.B., M.J.D., M.R., K.A.-A., J.C.H., D.D.G.), Department of Physiology (A.M.B., K.A.-A., D.D.G.), Department of Anesthesiology (J.K.F.), Department of Physical Medicine and Rehabilitation (M.J.D.), and Departments of Surgery, Cardiothoracic Surgery (M.G., C.K.R.), Medical College of Wisconsin, Milwaukee; Departments of Pharmacology and Physiology, New Jersey Medical School of Rutgers, Newark (P.G., J.H.S.); Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City (R.G.M., A.J.D.); and Shraga Segal Departments of Immunology and Microbiology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel (R.P., E.P.).
Michael RiedelFrom the Department of Medicine, Cardiovascular Center (A.M.B., M.J.D., M.R., K.A.-A., J.C.H., D.D.G.), Department of Physiology (A.M.B., K.A.-A., D.D.G.), Department of Anesthesiology (J.K.F.), Department of Physical Medicine and Rehabilitation (M.J.D.), and Departments of Surgery, Cardiothoracic Surgery (M.G., C.K.R.), Medical College of Wisconsin, Milwaukee; Departments of Pharmacology and Physiology, New Jersey Medical School of Rutgers, Newark (P.G., J.H.S.); Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City (R.G.M., A.J.D.); and Shraga Segal Departments of Immunology and Microbiology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel (R.P., E.P.).
Karima Ait-AissaFrom the Department of Medicine, Cardiovascular Center (A.M.B., M.J.D., M.R., K.A.-A., J.C.H., D.D.G.), Department of Physiology (A.M.B., K.A.-A., D.D.G.), Department of Anesthesiology (J.K.F.), Department of Physical Medicine and Rehabilitation (M.J.D.), and Departments of Surgery, Cardiothoracic Surgery (M.G., C.K.R.), Medical College of Wisconsin, Milwaukee; Departments of Pharmacology and Physiology, New Jersey Medical School of Rutgers, Newark (P.G., J.H.S.); Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City (R.G.M., A.J.D.); and Shraga Segal Departments of Immunology and Microbiology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel (R.P., E.P.).
Paula GreenFrom the Department of Medicine, Cardiovascular Center (A.M.B., M.J.D., M.R., K.A.-A., J.C.H., D.D.G.), Department of Physiology (A.M.B., K.A.-A., D.D.G.), Department of Anesthesiology (J.K.F.), Department of Physical Medicine and Rehabilitation (M.J.D.), and Departments of Surgery, Cardiothoracic Surgery (M.G., C.K.R.), Medical College of Wisconsin, Milwaukee; Departments of Pharmacology and Physiology, New Jersey Medical School of Rutgers, Newark (P.G., J.H.S.); Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City (R.G.M., A.J.D.); and Shraga Segal Departments of Immunology and Microbiology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel (R.P., E.P.).
Joseph C HockenberryFrom the Department of Medicine, Cardiovascular Center (A.M.B., M.J.D., M.R., K.A.-A., J.C.H., D.D.G.), Department of Physiology (A.M.B., K.A.-A., D.D.G.), Department of Anesthesiology (J.K.F.), Department of Physical Medicine and Rehabilitation (M.J.D.), and Departments of Surgery, Cardiothoracic Surgery (M.G., C.K.R.), Medical College of Wisconsin, Milwaukee; Departments of Pharmacology and Physiology, New Jersey Medical School of Rutgers, Newark (P.G., J.H.S.); Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City (R.G.M., A.J.D.); and Shraga Segal Departments of Immunology and Microbiology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel (R.P., E.P.).
R Garret MorganFrom the Department of Medicine, Cardiovascular Center (A.M.B., M.J.D., M.R., K.A.-A., J.C.H., D.D.G.), Department of Physiology (A.M.B., K.A.-A., D.D.G.), Department of Anesthesiology (J.K.F.), Department of Physical Medicine and Rehabilitation (M.J.D.), and Departments of Surgery, Cardiothoracic Surgery (M.G., C.K.R.), Medical College of Wisconsin, Milwaukee; Departments of Pharmacology and Physiology, New Jersey Medical School of Rutgers, Newark (P.G., J.H.S.); Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City (R.G.M., A.J.D.); and Shraga Segal Departments of Immunology and Microbiology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel (R.P., E.P.).
Anthony J DonatoFrom the Department of Medicine, Cardiovascular Center (A.M.B., M.J.D., M.R., K.A.-A., J.C.H., D.D.G.), Department of Physiology (A.M.B., K.A.-A., D.D.G.), Department of Anesthesiology (J.K.F.), Department of Physical Medicine and Rehabilitation (M.J.D.), and Departments of Surgery, Cardiothoracic Surgery (M.G., C.K.R.), Medical College of Wisconsin, Milwaukee; Departments of Pharmacology and Physiology, New Jersey Medical School of Rutgers, Newark (P.G., J.H.S.); Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City (R.G.M., A.J.D.); and Shraga Segal Departments of Immunology and Microbiology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel (R.P., E.P.).
Refael PelegFrom the Department of Medicine, Cardiovascular Center (A.M.B., M.J.D., M.R., K.A.-A., J.C.H., D.D.G.), Department of Physiology (A.M.B., K.A.-A., D.D.G.), Department of Anesthesiology (J.K.F.), Department of Physical Medicine and Rehabilitation (M.J.D.), and Departments of Surgery, Cardiothoracic Surgery (M.G., C.K.R.), Medical College of Wisconsin, Milwaukee; Departments of Pharmacology and Physiology, New Jersey Medical School of Rutgers, Newark (P.G., J.H.S.); Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City (R.G.M., A.J.D.); and Shraga Segal Departments of Immunology and Microbiology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel (R.P., E.P.).
Mario GasparriFrom the Department of Medicine, Cardiovascular Center (A.M.B., M.J.D., M.R., K.A.-A., J.C.H., D.D.G.), Department of Physiology (A.M.B., K.A.-A., D.D.G.), Department of Anesthesiology (J.K.F.), Department of Physical Medicine and Rehabilitation (M.J.D.), and Departments of Surgery, Cardiothoracic Surgery (M.G., C.K.R.), Medical College of Wisconsin, Milwaukee; Departments of Pharmacology and Physiology, New Jersey Medical School of Rutgers, Newark (P.G., J.H.S.); Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City (R.G.M., A.J.D.); and Shraga Segal Departments of Immunology and Microbiology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel (R.P., E.P.).
Chris K RokkasFrom the Department of Medicine, Cardiovascular Center (A.M.B., M.J.D., M.R., K.A.-A., J.C.H., D.D.G.), Department of Physiology (A.M.B., K.A.-A., D.D.G.), Department of Anesthesiology (J.K.F.), Department of Physical Medicine and Rehabilitation (M.J.D.), and Departments of Surgery, Cardiothoracic Surgery (M.G., C.K.R.), Medical College of Wisconsin, Milwaukee; Departments of Pharmacology and Physiology, New Jersey Medical School of Rutgers, Newark (P.G., J.H.S.); Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City (R.G.M., A.J.D.); and Shraga Segal Departments of Immunology and Microbiology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel (R.P., E.P.).
Janine H SantosFrom the Department of Medicine, Cardiovascular Center (A.M.B., M.J.D., M.R., K.A.-A., J.C.H., D.D.G.), Department of Physiology (A.M.B., K.A.-A., D.D.G.), Department of Anesthesiology (J.K.F.), Department of Physical Medicine and Rehabilitation (M.J.D.), and Departments of Surgery, Cardiothoracic Surgery (M.G., C.K.R.), Medical College of Wisconsin, Milwaukee; Departments of Pharmacology and Physiology, New Jersey Medical School of Rutgers, Newark (P.G., J.H.S.); Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City (R.G.M., A.J.D.); and Shraga Segal Departments of Immunology and Microbiology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel (R.P., E.P.).
Esther PrielFrom the Department of Medicine, Cardiovascular Center (A.M.B., M.J.D., M.R., K.A.-A., J.C.H., D.D.G.), Department of Physiology (A.M.B., K.A.-A., D.D.G.), Department of Anesthesiology (J.K.F.), Department of Physical Medicine and Rehabilitation (M.J.D.), and Departments of Surgery, Cardiothoracic Surgery (M.G., C.K.R.), Medical College of Wisconsin, Milwaukee; Departments of Pharmacology and Physiology, New Jersey Medical School of Rutgers, Newark (P.G., J.H.S.); Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City (R.G.M., A.J.D.); and Shraga Segal Departments of Immunology and Microbiology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel (R.P., E.P.).
David D GuttermanFrom the Department of Medicine, Cardiovascular Center (A.M.B., M.J.D., M.R., K.A.-A., J.C.H., D.D.G.), Department of Physiology (A.M.B., K.A.-A., D.D.G.), Department of Anesthesiology (J.K.F.), Department of Physical Medicine and Rehabilitation (M.J.D.), and Departments of Surgery, Cardiothoracic Surgery (M.G., C.K.R.), Medical College of Wisconsin, Milwaukee; Departments of Pharmacology and Physiology, New Jersey Medical School of Rutgers, Newark (P.G., J.H.S.); Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City (R.G.M., A.J.D.); and Shraga Segal Departments of Immunology and Microbiology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel (R.P., E.P.).
University of Utah · USRutgers New Jersey Medical SchoolRutgers, The State University of New Jersey · US

Funding

Vascular Signaling by Free RadicalsP01HL068769 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI ROMAN, RICHARD J. · 2002 to 2006
$7.2M
HYPERTENSION TRAINING GRANTT32HL007792 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI HARDER, DAVID RAE · 1994 to 2013
$3.7M
Novel Regulatory Mechanisms in the Human MicrocirculationR01HL135901 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI GUTTERMAN, DAVID D. · 2017 to 2020
$1.7M
Mechanism of Flow-Induced Dilation in the Human MicrocirculationR01HL113612 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI GUTTERMAN, DAVID D. · 2013 to 2016
$1.7M
Mechanisms of Caloric Restriction and Mimetic Vasoprotection in Old ArteriesR01AG040297 · NIA · UNIVERSITY OF UTAH · PI DONATO, ANTHONY JOHN · 2011 to 2015
$1.5M
Anesthesiology Research Training ProgramT32GM089586 · NIGMS · MEDICAL COLLEGE OF WISCONSIN · PI EBERT, THOMAS JAY · 2010 to 2019
$1.5M
Amelioration of aged endothelial dysfunction by NAMPT and caloric restrictionK02AG045339 · NIA · UNIVERSITY OF UTAH · PI DONATO, ANTHONY JOHN · 2014 to 2018
$558k
Differentiation of mitochondrial vs. nuclear function of telomeraseR21OD018306 · OD · MEDICAL COLLEGE OF WISCONSIN · PI BEYER, ANDREAS M · 2014 to 2015
$411k
Reversing Arterial Aging via mTOR Inhibition: AMPK Activation as a RapalogR21AG043952 · NIA · UNIVERSITY OF UTAH · PI DONATO, ANTHONY JOHN, LESNIEWSKI, LISA A · 2013 to 2014
$410k
NHLBI NIH HHS P01 HL068769NHLBI NIH HHS R01 HL113612NHLBI NIH HHS R01 HL135901NHLBI NIH HHS T32HL007792NIA NIH HHS K02 AG045339NIA NIH HHS R01 AG040297NIA NIH HHS R21 AG0443952NIGMS NIH HHS GM089586NIGMS NIH HHS T32 GM089586NIH HHS R21 OD018306
6 · The paper itself

Abstract

rationaleTelomerase is a nuclear regulator of telomere elongation with recent reports suggesting a role in regulation of mitochondrial reactive oxygen species. Flow-mediated dilation in patients with cardiovascular disease is dependent on the formation of reactive oxygen species.

objectiveWe examined the hypothesis that telomerase activity modulates microvascular flow-mediated dilation, and loss of telomerase activity contributes to the change of mediator from nitric oxide to mitochondrial hydrogen peroxide in patients with coronary artery disease (CAD). METHODS AND

resultsHuman coronary and adipose arterioles were isolated for videomicroscopy. Flow-mediated dilation was measured in vessels pretreated with the telomerase inhibitor BIBR-1532 or vehicle. Statistical differences between groups were determined using a 2-way analysis of variance repeated measure (n≥4; P<0.05). L-NAME (N(ω)-nitro-L-arginine methyl ester; nitric oxide synthase inhibitor) abolished flow-mediated dilation in arterioles from subjects without CAD, whereas polyethylene glycol-catalase (PEG-catalase; hydrogen peroxide scavenger) had no effect. After exposure to BIBR-1532, arterioles from non-CAD subjects maintained the magnitude of dilation but changed the mediator from nitric oxide to mitochondrial hydrogen peroxide (% max diameter at 100 cm H2O: vehicle 74.6±4.1, L-NAME 37.0±2.0*, PEG-catalase 82.1±2.8; BIBR-1532 69.9±4.0, L-NAME 84.7±2.2, PEG-catalase 36.5±6.9*). Conversely, treatment of microvessels from CAD patients with the telomerase activator AGS 499 converted the PEG-catalase-inhibitable dilation to one mediated by nitric oxide (% max diameter at 100 cm H2O: adipose, AGS 499 78.5±3.9; L-NAME 10.9±17.5*; PEG-catalase 79.2±4.9). Endothelial-independent dilation was not altered with either treatment.

conclusionsWe have identified a novel role for telomerase in re-establishing a physiological mechanism of vasodilation in arterioles from subjects with CAD. These findings suggest a new target for reducing the oxidative milieu in the microvasculature of patients with CAD.

Indexed as

Adipose TissueAgedArteriolesBlood Flow VelocityCells, CulturedCoronary Artery DiseaseCoronary VesselsEndothelium, VascularFemaleHumansHuman Umbilical Vein Endothelial CellsMaleMicrocirculationMiddle AgedTelomeraseVasodilationTelomerasecoronary artery diseaseflow-mediated dilationmicrovascular dysfunctionmitochondriareactive oxygen speciestelomerase activityvascular biology

Identifiers

PMID26699654
PMCPMC4772813
OpenAlexW2201138959

What OpenQuestion holds

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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.