Evidence map›Paper›PMID 26338300›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2015

Overexpression of Cardiomyocyte α1A-Adrenergic Receptors Attenuates Postinfarct Remodeling by Inducing Angiogenesis Through Heterocellular Signaling.

Xin Zhao, Poornima Balaji, Ronald Pachon, Daniella M Beniamen, Dorothy E Vatner, Robert M Graham, Stephen F Vatner

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

Article in Arteriosclerosis, thrombosis, and vascular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

21 citing papers in PubMed, 34 citations in OpenAlex.

  1. Article
  2. In silico pharmacology · 2026
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  5. Exosomes for angiogenesis induction in ischemic disorders.Journal of cellular and molecular medicine · 2023
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  6. αInternational journal of molecular sciences · 2023
    Review
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  9. Cardiac α1A-adrenergic receptors: emerging protective roles in cardiovascular diseases.American journal of physiology. Heart and circulatory physiology · 2021
    Review
  10. Current Developments on the Role of αFrontiers in cell and developmental biology · 2021
    Review
  11. Rats are protected from the stress of chronic pressure overload compared with mice.American journal of physiology. Regulatory, integrative and comparative physiology · 2020
    Article
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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

7 authors at 1 institution in 1 country.

Xin ZhaoFrom the Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, Rutgers-New Jersey Medical School, Newark (X.Z., R.P., D.E.V., S.F.V.); and Victor Chang Cardiac Research Institute and Faculty of Medicine and Life Sciences, University of New South Wales, Sydney, New South Wales, Australia (P.B., D.M.B., R.M.G.).
Poornima BalajiFrom the Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, Rutgers-New Jersey Medical School, Newark (X.Z., R.P., D.E.V., S.F.V.); and Victor Chang Cardiac Research Institute and Faculty of Medicine and Life Sciences, University of New South Wales, Sydney, New South Wales, Australia (P.B., D.M.B., R.M.G.).
Ronald PachonFrom the Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, Rutgers-New Jersey Medical School, Newark (X.Z., R.P., D.E.V., S.F.V.); and Victor Chang Cardiac Research Institute and Faculty of Medicine and Life Sciences, University of New South Wales, Sydney, New South Wales, Australia (P.B., D.M.B., R.M.G.).
Daniella M BeniamenFrom the Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, Rutgers-New Jersey Medical School, Newark (X.Z., R.P., D.E.V., S.F.V.); and Victor Chang Cardiac Research Institute and Faculty of Medicine and Life Sciences, University of New South Wales, Sydney, New South Wales, Australia (P.B., D.M.B., R.M.G.).
Dorothy E VatnerFrom the Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, Rutgers-New Jersey Medical School, Newark (X.Z., R.P., D.E.V., S.F.V.); and Victor Chang Cardiac Research Institute and Faculty of Medicine and Life Sciences, University of New South Wales, Sydney, New South Wales, Australia (P.B., D.M.B., R.M.G.).
Robert M GrahamFrom the Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, Rutgers-New Jersey Medical School, Newark (X.Z., R.P., D.E.V., S.F.V.); and Victor Chang Cardiac Research Institute and Faculty of Medicine and Life Sciences, University of New South Wales, Sydney, New South Wales, Australia (P.B., D.M.B., R.M.G.).
Stephen F VatnerFrom the Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, Rutgers-New Jersey Medical School, Newark (X.Z., R.P., D.E.V., S.F.V.); and Victor Chang Cardiac Research Institute and Faculty of Medicine and Life Sciences, University of New South Wales, Sydney, New South Wales, Australia (P.B., D.M.B., R.M.G.). vatnersf@njms.rutgers.edu b.graham@victorchang.edu.au.
Victor Chang Cardiac Research Institute · AU

Funding

Molecular Mechanisms in Chronically Stunned MyocardiumP01HL069020 · NHLBI · UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL · PI VATNER, DOROTHY EILEEN · 2001 to 2014
$21.3M
Skeletal Muscle Basis for Improved Exercise Endurance in RGS14 KOR01HL106511 · NHLBI · UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL · PI VATNER, STEPHEN F · 2011 to 2019
$3.8M
Integrative Mechanisms in Cardiovascular DiseaseT32HL069752 · NHLBI · UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL · PI VATNER, STEPHEN F · 2004 to 2013
$2.9M
RGS 14 Disruption, Vascular Effects Leading to CardioprotectionR01HL124282 · NHLBI · RBHS-NEW JERSEY MEDICAL SCHOOL · PI VATNER, STEPHEN F · 2015 to 2018
$2.4M
Adenylyl cyclase isoforms in hypertrophy and heart failureR01HL093481 · NHLBI · UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL · PI VATNER, STEPHEN F · 2009 to 2013
$2.3M
SFRP2, cell survival, and coronary vascular angiogenesisR01HL119464 · NHLBI · RBHS-NEW JERSEY MEDICAL SCHOOL · PI VATNER, DOROTHY EILEEN · 2013 to 2016
$1.8M
NHLBI NIH HHS 1R01HL124282NHLBI NIH HHS 3P01HL069020NHLBI NIH HHS 5R01HL106511NHLBI NIH HHS 5R01HL119464NHLBI NIH HHS 6R01HL093481NHLBI NIH HHS 6T32HL069752NHLBI NIH HHS P01 HL069020NHLBI NIH HHS R01 HL093481NHLBI NIH HHS R01 HL106511NHLBI NIH HHS R01 HL119464NHLBI NIH HHS R01 HL124282NHLBI NIH HHS T32 HL069752
6 · The paper itself

Abstract

objectiveStimulation of cardiac α1A-adrenergic receptors (α1A-AR) has been proposed for treatment of heart failure, since it increases myocardial contractility. We investigated a different mechanism, induction of angiogenesis. APPROACH AND

resultsFour to 6 weeks after permanent coronary artery occlusion, transgenic rats with cardiomyocyte-specific α1A-adrenergic receptor overexpression had less remodeling than their nontransgenic littermates, with less fibrosis, hypertrophy and lung weight, and preserved left ventricular ejection fraction and wall stress (all P<0.05). Coronary blood flow, measured with microspheres, increased in the infarct zone in transgenic rats compared with nontransgenic littermates (1.4±0.2 versus 0.5±0.08 mL min(-1) g(-1); P<0.05), which is consistent with angiogenesis, as reflected by a 20% increase in capillary density in the zone adjacent to the infarct. The question arose, how does transgenic overexpression of a gene in cardiomyocytes induce angiogenesis? We identified a paracrine mechanism, whereby vascular endothelial growth factor-A mRNA and protein were increased in isolated transgenic cardiomyocytes and also by nontransgenic littermate cardiomyocytes treated with an α1A-agonist, resulting in angiogenesis. Conditioned medium from cultured cardiomyocytes treated with an α1A agonist enhanced human umbilical vein endothelial cell tubule formation, which was blocked by an anti-vascular endothelial growth factor-A antibody. Moreover, improved cardiac function, blood flow, and increased capillary density after chronic coronary artery occlusion in transgenic rats were blocked by either a mitogen ERK kinase (MEK) or a vascular endothelial growth factor-A inhibitor.

conclusionCardiomyocyte-specific overexpression of the α1A-adrenergic receptors resulted in enhanced MEK-dependent cardiomyocyte vascular endothelial growth factor-A expression, which stimulates angiogenesis via a paracrine mechanism involving heterocellular cardiomyocyte/endothelial cell signaling, protecting against remodeling and heart failure after chronic coronary artery occlusion.

Indexed as

Neovascularization, PhysiologicVentricular RemodelingAngiogenesis InhibitorsAnimalsCells, CulturedDisease Models, AnimalFibrosisHumansHuman Umbilical Vein Endothelial CellsMAP Kinase Kinase KinasesMice, TransgenicMyocardial ContractionMyocardial InfarctionMyocytes, CardiacParacrine CommunicationProtein Kinase InhibitorsAngiogenesis InhibitorsMAP Kinase Kinase KinasesProtein Kinase InhibitorsReceptors, Adrenergic, alpha-1Vascular Endothelial Growth Factor Avascular endothelial growth factor A, mousevascular endothelial growth factor A, ratalpha adrenergic receptorsangiogenesiscardiacheart failuremyocardial infarctionmyocytesvascular endothelial growth factor

Identifiers

PMID26338300
PMCPMC4618777
OpenAlexW1956788884

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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.