Evidence map›Paper›PMID 25278290›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2014

Identification of small proline-rich repeat protein 3 as a novel atheroprotective factor that promotes adaptive Akt signaling in vascular smooth muscle cells.

Amanda K Segedy, Amy L Pyle, Bin Li, Youmin Zhang, Vladimir R Babaev, Parmjit Jat, Sergio Fazio, James B Atkinson, MacRae F Linton, Pampee P Young

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

Article in Arteriosclerosis, thrombosis, and vascular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.2field-weighted citation impact, top 41% 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

10 citing papers in PubMed, 13 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Small proline-rich repeat 3 is a novel coordinator of PDGFRβ and integrin β1 crosstalk to augment proliferation and matrix synthesis by cardiac fibroblasts.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020
    Article
  8. Article
  9. Article
  10. Atherosclerosis.Arteriosclerosis, thrombosis, and vascular biology · 2015
    Review
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

10 authors at 3 institutions in 2 countries.

Amanda K SegedyFrom the Department of Pathology, Microbiology, and Immunology (A.K.S., B.L., S.F., J.B.A., P.P.Y.) and Departments of Veterans Affairs Medical Center (J.B.A., P.P.Y.), Pharmacology (M.F.L.), and Medicine (Y.Z., V.R.B., S.F., M.F.L., P.P.Y.), Vanderbilt University Medical Center, Nashville, TN; Department of Neurodegenerative Diseases, Institute of Neurology, University College London, Queen Square, London, United Kingdom (P.J.); Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH (A.L.P.); and Department of Pathology, The Ohio State University, Columbus (A.L.P.).
Amy L PyleFrom the Department of Pathology, Microbiology, and Immunology (A.K.S., B.L., S.F., J.B.A., P.P.Y.) and Departments of Veterans Affairs Medical Center (J.B.A., P.P.Y.), Pharmacology (M.F.L.), and Medicine (Y.Z., V.R.B., S.F., M.F.L., P.P.Y.), Vanderbilt University Medical Center, Nashville, TN; Department of Neurodegenerative Diseases, Institute of Neurology, University College London, Queen Square, London, United Kingdom (P.J.); Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH (A.L.P.); and Department of Pathology, The Ohio State University, Columbus (A.L.P.).
Bin LiFrom the Department of Pathology, Microbiology, and Immunology (A.K.S., B.L., S.F., J.B.A., P.P.Y.) and Departments of Veterans Affairs Medical Center (J.B.A., P.P.Y.), Pharmacology (M.F.L.), and Medicine (Y.Z., V.R.B., S.F., M.F.L., P.P.Y.), Vanderbilt University Medical Center, Nashville, TN; Department of Neurodegenerative Diseases, Institute of Neurology, University College London, Queen Square, London, United Kingdom (P.J.); Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH (A.L.P.); and Department of Pathology, The Ohio State University, Columbus (A.L.P.).
Youmin ZhangFrom the Department of Pathology, Microbiology, and Immunology (A.K.S., B.L., S.F., J.B.A., P.P.Y.) and Departments of Veterans Affairs Medical Center (J.B.A., P.P.Y.), Pharmacology (M.F.L.), and Medicine (Y.Z., V.R.B., S.F., M.F.L., P.P.Y.), Vanderbilt University Medical Center, Nashville, TN; Department of Neurodegenerative Diseases, Institute of Neurology, University College London, Queen Square, London, United Kingdom (P.J.); Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH (A.L.P.); and Department of Pathology, The Ohio State University, Columbus (A.L.P.).
Vladimir R BabaevFrom the Department of Pathology, Microbiology, and Immunology (A.K.S., B.L., S.F., J.B.A., P.P.Y.) and Departments of Veterans Affairs Medical Center (J.B.A., P.P.Y.), Pharmacology (M.F.L.), and Medicine (Y.Z., V.R.B., S.F., M.F.L., P.P.Y.), Vanderbilt University Medical Center, Nashville, TN; Department of Neurodegenerative Diseases, Institute of Neurology, University College London, Queen Square, London, United Kingdom (P.J.); Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH (A.L.P.); and Department of Pathology, The Ohio State University, Columbus (A.L.P.).
Parmjit JatFrom the Department of Pathology, Microbiology, and Immunology (A.K.S., B.L., S.F., J.B.A., P.P.Y.) and Departments of Veterans Affairs Medical Center (J.B.A., P.P.Y.), Pharmacology (M.F.L.), and Medicine (Y.Z., V.R.B., S.F., M.F.L., P.P.Y.), Vanderbilt University Medical Center, Nashville, TN; Department of Neurodegenerative Diseases, Institute of Neurology, University College London, Queen Square, London, United Kingdom (P.J.); Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH (A.L.P.); and Department of Pathology, The Ohio State University, Columbus (A.L.P.).
Sergio FazioFrom the Department of Pathology, Microbiology, and Immunology (A.K.S., B.L., S.F., J.B.A., P.P.Y.) and Departments of Veterans Affairs Medical Center (J.B.A., P.P.Y.), Pharmacology (M.F.L.), and Medicine (Y.Z., V.R.B., S.F., M.F.L., P.P.Y.), Vanderbilt University Medical Center, Nashville, TN; Department of Neurodegenerative Diseases, Institute of Neurology, University College London, Queen Square, London, United Kingdom (P.J.); Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH (A.L.P.); and Department of Pathology, The Ohio State University, Columbus (A.L.P.).
James B AtkinsonFrom the Department of Pathology, Microbiology, and Immunology (A.K.S., B.L., S.F., J.B.A., P.P.Y.) and Departments of Veterans Affairs Medical Center (J.B.A., P.P.Y.), Pharmacology (M.F.L.), and Medicine (Y.Z., V.R.B., S.F., M.F.L., P.P.Y.), Vanderbilt University Medical Center, Nashville, TN; Department of Neurodegenerative Diseases, Institute of Neurology, University College London, Queen Square, London, United Kingdom (P.J.); Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH (A.L.P.); and Department of Pathology, The Ohio State University, Columbus (A.L.P.).
MacRae F LintonFrom the Department of Pathology, Microbiology, and Immunology (A.K.S., B.L., S.F., J.B.A., P.P.Y.) and Departments of Veterans Affairs Medical Center (J.B.A., P.P.Y.), Pharmacology (M.F.L.), and Medicine (Y.Z., V.R.B., S.F., M.F.L., P.P.Y.), Vanderbilt University Medical Center, Nashville, TN; Department of Neurodegenerative Diseases, Institute of Neurology, University College London, Queen Square, London, United Kingdom (P.J.); Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH (A.L.P.); and Department of Pathology, The Ohio State University, Columbus (A.L.P.).
Pampee P YoungFrom the Department of Pathology, Microbiology, and Immunology (A.K.S., B.L., S.F., J.B.A., P.P.Y.) and Departments of Veterans Affairs Medical Center (J.B.A., P.P.Y.), Pharmacology (M.F.L.), and Medicine (Y.Z., V.R.B., S.F., M.F.L., P.P.Y.), Vanderbilt University Medical Center, Nashville, TN; Department of Neurodegenerative Diseases, Institute of Neurology, University College London, Queen Square, London, United Kingdom (P.J.); Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH (A.L.P.); and Department of Pathology, The Ohio State University, Columbus (A.L.P.). pampee.young@vanderbilt.edu.
National Hospital for Neurology and Neurosurgery · GBUniversity College London · GBNationwide Children's Hospital · US

Funding

VANDERBILT UNIVERSITY CTSA FOR PEDIATRIC RESEARCHUL1RR024975 · NCRR · VANDERBILT UNIVERSITY · PI BERNARD, GORDON RAPHAEL · 2007 to 2011
$45.7M
Vanderbilt Mouse Metabolic Physiology CenterU24DK059637 · NIDDK · VANDERBILT UNIVERSITY · PI WASSERMAN, DAVID H · 2001 to 2015
$14.9M
Vanderbilt Mouse Metabolic Phenotyping CenterU2CDK059637 · NIDDK · VANDERBILT UNIVERSITY · PI WASSERMAN, DAVID H · 2016 to 2021
$6.3M
FUNCTIONAL HIERARCHY OF REMNANT LIPOPROTEIN RECEPTORSR01HL057986 · NHLBI · VANDERBILT UNIVERSITY · PI FAZIO, SERGIO · 1998 to 2016
$6.2M
Creating Super Stem Cells for Cardiac and Wound RepairR01HL088424 · NHLBI · VANDERBILT UNIVERSITY · PI YOUNG, PAMPEE P · 2008 to 2012
$1.9M
Macrophage Akt and IKKalpha signaling in apoptosis and atherosclerosisR01HL105375 · NHLBI · VANDERBILT UNIVERSITY · PI LINTON, MACRAE F · 2010 to 2013
$1.8M
Uncovering Novel Atheroprotective MechanismsI01BX002337 · VA · VETERANS HEALTH ADMINISTRATION · PI YOUNG, PAMPEE P · 2014 to 2017
–
BLRD VA I01 BX002337NCRR NIH HHS UL1 RR024975NCRR NIH HHS UL1 RR024975-01NHLBI NIH HHS HL105375NHLBI NIH HHS HL57986NHLBI NIH HHS R01 HL057986NHLBI NIH HHS R01 HL088424NHLBI NIH HHS R01 HL105375NIDDK NIH HHS DK59637NIDDK NIH HHS U24 DK059637
6 · The paper itself

Abstract

objectiveAtherosclerosis is the primary driver of cardiovascular disease, the leading cause of death worldwide. Identification of naturally occurring atheroprotective genes has become a major goal for the development of interventions that will limit atheroma progression and associated adverse events. To this end, we have identified small proline-rich repeat protein (SPRR3) as selectively upregulated in vascular smooth muscle cells (VSMCs) of atheroma-bearing arterial tissue versus healthy arterial tissue. In this study, we sought to determine the role of SPRR3 in atheroma pathophysiology. APPROACH AND

resultsWe found that atheroprone apolipoprotein E-null mice lacking SPRR3 developed significantly greater atheroma burden. To determine the cellular driver(s) of this increase, we evaluated SPRR3-dependent changes in bone marrow-derived cells, endothelial cells, and VSMCs. Bone marrow transplant of SPRR3-expressing cells into SPRR3(-/-)apolipoprotein E-deficient recipients failed to rescue atheroma burden. Similarly, endothelial cells did not exhibit a response to SPRR3 loss. However, atheromas from SPRR3-deficient mice exhibited increased TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling)-positive VSMCs compared with control. Cell death in SPRR3-deficient VSMCs was significantly increased in vitro. Conversely, SPRR3-overexpressing VSMCs exhibited reduced apoptosis compared with control. We also observed a PI3K (phosphatidylinositol 3-kinase)/Akt-dependent positive association between SPRR3 expression and levels of active Akt in VSMCs. The survival advantage seen in SPRR3-overexpressing VSMCs was abrogated after the addition of a PI3K/Akt pathway inhibitor.

conclusionsThese results indicate that SPRR3 protects the lesion from VSMC loss by promoting survival signaling in plaque VSMCs, thereby significantly decreasing atherosclerosis progression. As the first identified atheroma-specific VSMC prosurvival factor, SPRR3 represents a potential target for lesion-specific modulation of VSMC survival.

Indexed as

Adaptation, PhysiologicalAnimalsApolipoproteins EApoptosisAtherosclerosisCell ProliferationCell SurvivalCornified Envelope Proline-Rich ProteinsDisease ProgressionEndothelial CellsFemaleMacrophagesMaleMiceMice, Inbred C57BLMice, KnockoutApolipoproteins ECornified Envelope Proline-Rich ProteinsProto-Oncogene Proteins c-aktakt Proto-Oncogene Proteinatherosclerosismuscle, smooth, vascular

Identifiers

PMID25278290
PMCPMC4239161
OpenAlexW2161535895

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.