Evidence map›Paper›PMID 25669938›Full record

ArticleCirculation. Heart failure2015

Loss of secreted frizzled-related protein-1 leads to deterioration of cardiac function in mice and plays a role in human cardiomyopathy.

Piotr Sklepkiewicz, Takayuki Shiomi, Rajbir Kaur, Jie Sun, Susan Kwon, Becky Mercer, Peter Bodine, Ralph Theo Schermuly, Isaac George, P Christian Schulze and 1 more

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

Article in Circulation. Heart failure, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
3.2field-weighted citation impact, top 8% 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

42 citing papers in PubMed, 68 citations in OpenAlex.

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  16. The Pathogenesis of Cardiac Fibrosis: A Review of Recent Progress.International journal of molecular sciences · 2022
    Review
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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

11 authors at 1 institution in 1 country.

Piotr SklepkiewiczFrom the Center for Molecular Pulmonary Disease, Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, New York, NY (P.S., T.S., R.K., J.S., S.K., B.M., J.M.D.); Women's Health Research Institute, Department of Osteoporosis, Wyeth Research, Collegeville, PA (P.B.); Max Planck Institute, Department of Pathophysiology and Pulmonary, Bad Nauheim, Germany (R.T.S.); Center for Advanced Cardiac Care, Columbia University Medical Center, New York, NY (C.S.); and Division of Cardiothoracic Surgery, Department of Surgery, New York Presbyterian Hospital/Columbia University Medical Center, New York, NY (I.G.).
Takayuki ShiomiFrom the Center for Molecular Pulmonary Disease, Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, New York, NY (P.S., T.S., R.K., J.S., S.K., B.M., J.M.D.); Women's Health Research Institute, Department of Osteoporosis, Wyeth Research, Collegeville, PA (P.B.); Max Planck Institute, Department of Pathophysiology and Pulmonary, Bad Nauheim, Germany (R.T.S.); Center for Advanced Cardiac Care, Columbia University Medical Center, New York, NY (C.S.); and Division of Cardiothoracic Surgery, Department of Surgery, New York Presbyterian Hospital/Columbia University Medical Center, New York, NY (I.G.).
Rajbir KaurFrom the Center for Molecular Pulmonary Disease, Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, New York, NY (P.S., T.S., R.K., J.S., S.K., B.M., J.M.D.); Women's Health Research Institute, Department of Osteoporosis, Wyeth Research, Collegeville, PA (P.B.); Max Planck Institute, Department of Pathophysiology and Pulmonary, Bad Nauheim, Germany (R.T.S.); Center for Advanced Cardiac Care, Columbia University Medical Center, New York, NY (C.S.); and Division of Cardiothoracic Surgery, Department of Surgery, New York Presbyterian Hospital/Columbia University Medical Center, New York, NY (I.G.).
Jie SunFrom the Center for Molecular Pulmonary Disease, Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, New York, NY (P.S., T.S., R.K., J.S., S.K., B.M., J.M.D.); Women's Health Research Institute, Department of Osteoporosis, Wyeth Research, Collegeville, PA (P.B.); Max Planck Institute, Department of Pathophysiology and Pulmonary, Bad Nauheim, Germany (R.T.S.); Center for Advanced Cardiac Care, Columbia University Medical Center, New York, NY (C.S.); and Division of Cardiothoracic Surgery, Department of Surgery, New York Presbyterian Hospital/Columbia University Medical Center, New York, NY (I.G.).
Susan KwonFrom the Center for Molecular Pulmonary Disease, Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, New York, NY (P.S., T.S., R.K., J.S., S.K., B.M., J.M.D.); Women's Health Research Institute, Department of Osteoporosis, Wyeth Research, Collegeville, PA (P.B.); Max Planck Institute, Department of Pathophysiology and Pulmonary, Bad Nauheim, Germany (R.T.S.); Center for Advanced Cardiac Care, Columbia University Medical Center, New York, NY (C.S.); and Division of Cardiothoracic Surgery, Department of Surgery, New York Presbyterian Hospital/Columbia University Medical Center, New York, NY (I.G.).
Becky MercerFrom the Center for Molecular Pulmonary Disease, Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, New York, NY (P.S., T.S., R.K., J.S., S.K., B.M., J.M.D.); Women's Health Research Institute, Department of Osteoporosis, Wyeth Research, Collegeville, PA (P.B.); Max Planck Institute, Department of Pathophysiology and Pulmonary, Bad Nauheim, Germany (R.T.S.); Center for Advanced Cardiac Care, Columbia University Medical Center, New York, NY (C.S.); and Division of Cardiothoracic Surgery, Department of Surgery, New York Presbyterian Hospital/Columbia University Medical Center, New York, NY (I.G.).
Peter BodineFrom the Center for Molecular Pulmonary Disease, Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, New York, NY (P.S., T.S., R.K., J.S., S.K., B.M., J.M.D.); Women's Health Research Institute, Department of Osteoporosis, Wyeth Research, Collegeville, PA (P.B.); Max Planck Institute, Department of Pathophysiology and Pulmonary, Bad Nauheim, Germany (R.T.S.); Center for Advanced Cardiac Care, Columbia University Medical Center, New York, NY (C.S.); and Division of Cardiothoracic Surgery, Department of Surgery, New York Presbyterian Hospital/Columbia University Medical Center, New York, NY (I.G.).
Ralph Theo SchermulyFrom the Center for Molecular Pulmonary Disease, Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, New York, NY (P.S., T.S., R.K., J.S., S.K., B.M., J.M.D.); Women's Health Research Institute, Department of Osteoporosis, Wyeth Research, Collegeville, PA (P.B.); Max Planck Institute, Department of Pathophysiology and Pulmonary, Bad Nauheim, Germany (R.T.S.); Center for Advanced Cardiac Care, Columbia University Medical Center, New York, NY (C.S.); and Division of Cardiothoracic Surgery, Department of Surgery, New York Presbyterian Hospital/Columbia University Medical Center, New York, NY (I.G.).
Isaac GeorgeFrom the Center for Molecular Pulmonary Disease, Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, New York, NY (P.S., T.S., R.K., J.S., S.K., B.M., J.M.D.); Women's Health Research Institute, Department of Osteoporosis, Wyeth Research, Collegeville, PA (P.B.); Max Planck Institute, Department of Pathophysiology and Pulmonary, Bad Nauheim, Germany (R.T.S.); Center for Advanced Cardiac Care, Columbia University Medical Center, New York, NY (C.S.); and Division of Cardiothoracic Surgery, Department of Surgery, New York Presbyterian Hospital/Columbia University Medical Center, New York, NY (I.G.).
P Christian SchulzeFrom the Center for Molecular Pulmonary Disease, Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, New York, NY (P.S., T.S., R.K., J.S., S.K., B.M., J.M.D.); Women's Health Research Institute, Department of Osteoporosis, Wyeth Research, Collegeville, PA (P.B.); Max Planck Institute, Department of Pathophysiology and Pulmonary, Bad Nauheim, Germany (R.T.S.); Center for Advanced Cardiac Care, Columbia University Medical Center, New York, NY (C.S.); and Division of Cardiothoracic Surgery, Department of Surgery, New York Presbyterian Hospital/Columbia University Medical Center, New York, NY (I.G.).
Jeanine M D'ArmientoFrom the Center for Molecular Pulmonary Disease, Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, New York, NY (P.S., T.S., R.K., J.S., S.K., B.M., J.M.D.); Women's Health Research Institute, Department of Osteoporosis, Wyeth Research, Collegeville, PA (P.B.); Max Planck Institute, Department of Pathophysiology and Pulmonary, Bad Nauheim, Germany (R.T.S.); Center for Advanced Cardiac Care, Columbia University Medical Center, New York, NY (C.S.); and Division of Cardiothoracic Surgery, Department of Surgery, New York Presbyterian Hospital/Columbia University Medical Center, New York, NY (I.G.). jmd12@cumc.columbia.edu.
Columbia University Irving Medical Center · US

Funding

Smoke Induced Airway Injury in the LungR01HL086936 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI D'ARMIENTO, JEANINE M · 2007 to 2016
$3.7M
Cardiac Lipotoxicity and Ceramide Metabolism in Heart FailureR01HL114813 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI COLOMBO, PAOLO C, SCHULZE, P. CHRISTIAN · 2013 to 2017
$3.0M
Inducible Macrophage Specific Gene Expression in DiseasesRC1HL100384 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI D'ARMIENTO, JEANINE M · 2009 to 2010
$969k
ALTERED MATRIX METALLOPROTEINASES IN HEART FAILURER01AG016994 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI D'ARMIENTO, JEANINE M · 1998 to 2002
$895k
NHLBI NIH HHS R01 HL086936NHLBI NIH HHS R01-HL086936NHLBI NIH HHS R01-HL100384NHLBI NIH HHS R01 HL114813NHLBI NIH HHS RC1 HL100384NIA NIH HHS R01 AG016994
6 · The paper itself

Abstract

backgroundThe Wnt/β-catenin signaling pathway plays a central role during cardiac development and has been implicated in cardiac remodeling and aging. However, the role of Wnt modulators in this process is unknown. In this study, we examined the role of the Wnt signaling inhibitor secreted frizzled-related protein-1 (sFRP-1) in aged wild-type and sFRP-1-deficient mice. METHODS AND

resultssFRP-1 gene deletion mice were grossly normal with no difference in mortality but developed abnormal cardiac structure and dysfunction with progressive age. Ventricular dilation and hypertrophy in addition to deterioration of cardiac function and massive cardiac fibrosis, all features present in dilated cardiomyopathy, were observed in the aged sFRP-1 knockout mice. Loss of sFRP-1 led to increased expression of Wnt ligands (Wnt1, 3, 7b, and 16) and Wnt target genes (Wisp1 and Lef1) in aged hearts, which correlated with increased protein levels of β-catenin. Cardiac fibroblasts lacking endogenous sFRP-1 showed increased α-smooth muscle actin expression, higher cell proliferation rates, and increased collagen production consistent with the cardiac phenotype exhibited in aged sFRP-1 knockout mice. The clinical relevance of these findings was supported by the demonstration of decreased sFRP-1 gene expression and increased Wisp-1 levels in the left ventricles of patients with ischemic dilated cardiomyopathy and dilated cardiomyopathy.

conclusionsThis study identifies a novel role of sFRP-1 in age-related cardiac deterioration and fibrosis. Further exploration of this pathway will identify downstream molecules important in these processes and also suggest the potential use of Wnt signaling agents as therapeutic targets for age-related cardiovascular disorders in humans.

Indexed as

AnimalsCardiomyopathy, DilatedCellular SenescenceFibrosisGene Expression ProfilingHemodynamicsHumansImmunohistochemistryIntercellular Signaling Peptides and ProteinsMembrane ProteinsMiceMice, KnockoutMyocardiumSecreted Frizzled-Related ProteinsWnt Signaling PathwayIntercellular Signaling Peptides and ProteinsMembrane ProteinsSecreted Frizzled-Related ProteinsSfrp1 protein, mousecardiomyopathy, dilatedfibrosisheartWnt signaling pathway

Identifiers

PMID25669938
PMCPMC4405910
OpenAlexW2166332974

What OpenQuestion holds

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Read underepoch 390

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.