Evidence map›Paper›PMID 35157519›Full record

ArticleCirculation2022

Prothymosin Alpha: A Novel Contributor to Estradiol Receptor Alpha-Mediated CD8

Livia S A Passos, Prabhash K Jha, Dakota Becker-Greene, Mark C Blaser, Dayanna Romero, Adrien Lupieri, Galina K Sukhova, Peter Libby, Sasha A Singh, Walderez O Dutra and 4 more

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

Article in Circulation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 2 pooled it
7.4field-weighted citation impact, top 2% 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

32 citing papers in PubMed, 2 syntheses or guidelines pooled it, 41 citations in OpenAlex.

  1. Pooled it
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  8. Valve biology and rheumatic heart disease pathogenesis.Nature cardiovascular research · 2026
    Review
  9. Acute rheumatic fever and rheumatic heart disease.Nature reviews. Disease primers · 2026
    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

14 authors at 4 institutions in 3 countries.

Livia S A PassosCenter for Excellence in Vascular Biology (L.S.A.P., P.K.J., D.B.-G., D.R., A.L., G.K.S., P.L., M.A., E.A.), Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0002-5725-5691
Prabhash K JhaCenter for Excellence in Vascular Biology (L.S.A.P., P.K.J., D.B.-G., D.R., A.L., G.K.S., P.L., M.A., E.A.), Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Dakota Becker-GreeneCenter for Excellence in Vascular Biology (L.S.A.P., P.K.J., D.B.-G., D.R., A.L., G.K.S., P.L., M.A., E.A.), Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Mark C BlaserCenter for Interdisciplinary Cardiovascular Sciences (M.C.B., S.A.S., M.A., E.A.), Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0002-3923-9786
Dayanna RomeroCenter for Excellence in Vascular Biology (L.S.A.P., P.K.J., D.B.-G., D.R., A.L., G.K.S., P.L., M.A., E.A.), Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Adrien LupieriCenter for Excellence in Vascular Biology (L.S.A.P., P.K.J., D.B.-G., D.R., A.L., G.K.S., P.L., M.A., E.A.), Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0002-9245-0169
Galina K SukhovaCenter for Excellence in Vascular Biology (L.S.A.P., P.K.J., D.B.-G., D.R., A.L., G.K.S., P.L., M.A., E.A.), Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0002-1421-9455
Peter LibbyCenter for Excellence in Vascular Biology (L.S.A.P., P.K.J., D.B.-G., D.R., A.L., G.K.S., P.L., M.A., E.A.), Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0002-1502-502X
Sasha A SinghCenter for Interdisciplinary Cardiovascular Sciences (M.C.B., S.A.S., M.A., E.A.), Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Walderez O DutraDepartamento de Morfologia, Instituto de Ciências Biológicas (W.O.D.), Federal University of Minas Gerais, Belo Horizonte, Brazil.
Masanori AikawaCenter for Excellence in Vascular Biology (L.S.A.P., P.K.J., D.B.-G., D.R., A.L., G.K.S., P.L., M.A., E.A.), Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0002-9275-2079
Robert A LevineCardiac Ultrasound Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston (R.A.L.).
Maria C P NunesHospital das Clinicas, School of Medicine (M.C.P.N.), Federal University of Minas Gerais, Belo Horizonte, Brazil.ORCID 0000-0001-8801-1828
Elena AikawaCenter for Excellence in Vascular Biology (L.S.A.P., P.K.J., D.B.-G., D.R., A.L., G.K.S., P.L., M.A., E.A.), Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0002-5725-5691
Brigham and Women's Hospital · USHospital das Clínicas da Universidade Federal de Minas Gerais · BRMassachusetts General Hospital · USUniversidade Federal de Minas Gerais · BR

Funding

Improving Mitral Compensation In Ischemic RegurgitationR01HL141917 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI AIKAWA, ELENA, BISCHOFF, JOYCE E. · 2018 to 2021
$5.6M
Macrophage-derived microcalcificaitonsR01HL136431 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI AIKAWA, ELENA · 2017 to 2020
$2.7M
New driver of fibrosis and calcification in CAVDR01HL147095 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI AIKAWA, ELENA · 2019 to 2022
$2.4M
NHLBI NIH HHS R01 HL136431NHLBI NIH HHS R01 HL141917NHLBI NIH HHS R01 HL147095
6 · The paper itself

Abstract

backgroundRheumatic heart valve disease (RHVD) is a leading cause of cardiovascular death in low- and middle-income countries and affects predominantly women. The underlying mechanisms of chronic valvular damage remain unexplored and regulators of sex predisposition are unknown.

methodsProteomics analysis of human heart valves (nondiseased aortic valves, nondiseased mitral valves [NDMVs], valves from patients with rheumatic aortic valve disease, and valves from patients with rheumatic mitral valve disease; n=30) followed by system biology analysis identified ProTα (prothymosin alpha) as a protein associated with RHVD. Histology, multiparameter flow cytometry, and enzyme-linked immunosorbent assay confirmed the expression of ProTα. In vitro experiments using peripheral mononuclear cells and valvular interstitial cells were performed using multiparameter flow cytometry and quantitative polymerase chain reaction. In silico analysis of the RHVD and

resultsA comparison of NDMV and nondiseased aortic valve proteomes established the baseline differences between nondiseased aortic and mitral valves. Thirteen unique proteins were enriched in NDMVs. Comparison of NDMVs versus valves from patients with rheumatic mitral valve disease and nondiseased aortic valves versus valves from patients with rheumatic aortic valve disease identified 213 proteins enriched in rheumatic valves. The expression of the 13 NDMV-enriched proteins was evaluated across the 213 proteins enriched in diseased valves, resulting in the discovery of ProTα common to valves from patients with rheumatic mitral valve disease and valves from patients with rheumatic aortic valve disease. ProTα plasma levels were significantly higher in patients with RHVD than in healthy individuals. Immunoreactive ProTα colocalized with CD8

conclusionsProTα-dependent CD8

Indexed as

Amino Acid SequenceCD8-Positive T-LymphocytesCollagen Type IComputational BiologyDisease SusceptibilityEpitopes, T-LymphocyteEstrogen Receptor alphaHeart Valve DiseasesHistocompatibility Antigens Class IHumansLeukocytes, MononuclearModels, BiologicalModels, MolecularProtein BindingProtein PrecursorsProteomeCollagen Type IEpitopes, T-LymphocyteESR1 protein, humanEstrogen Receptor alphaHistocompatibility Antigens Class IProtein PrecursorsProteomeprothymosin alphaThymosinautoimmunityheart valve diseasesrheumatic diseasesT-lymphocytes

Identifiers

PMID35157519
PMCPMC8869797
OpenAlexW4212866948

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.