Evidence map›Paper›PMID 30799229›Full record

ArticleDevelopmental cell2019

Endocardially Derived Macrophages Are Essential for Valvular Remodeling.

Ayako Shigeta, Vincent Huang, Jonathan Zuo, Rana Besada, Yasuhiro Nakashima, Yan Lu, Yichen Ding, Matteo Pellegrini, Rajan P Kulkarni, Tzung Hsiai and 4 more

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

Article in Developmental cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed
6.7field-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

51 citing papers in PubMed, 89 citations in OpenAlex.

  1. Article
  2. Review
  3. Macrophages in embryonic development.Nature reviews. Immunology · 2026
    Review
  4. Immune Mechanisms of Heart Valve Development, Homeostasis, and Disease.Arteriosclerosis, thrombosis, and vascular biology · 2026
    Review
  5. Review
  6. Review
  7. Immune-mediated cardiac development and regeneration.Seminars in cell & developmental biology · 2025
    Review
  8. Review
  9. Review
  10. Maternal Immune Activation: Implications for Congenital Heart Defects.Clinical reviews in allergy & immunology · 2025
    Review
  11. Article
  12. Article
  13. The molecular mechanisms of cardiac development and related diseases.Signal transduction and targeted therapy · 2024
    Review
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Increased cardiac macrophages inFrontiers in genetics · 2024
    Article
  20. Macrophage lineages in heart development and regeneration.Current topics in developmental biology · 2024
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 2 institutions in 1 country.

Ayako ShigetaDepartment of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Vincent HuangDepartment of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Jonathan ZuoDepartment of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Rana BesadaDepartment of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Yasuhiro NakashimaDepartment of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Yan LuDivision of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Yichen DingDivision of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Matteo PellegriniDepartment of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Rajan P KulkarniDivision of Dermatology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Tzung HsiaiDivision of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Arjun DebDepartment of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Bin ZhouDepartment of Genetics, Pediatrics, and Medicine (Cardiology), Albert Einstein College of Medicine, New York, NY 10461, USA.
Haruko NakanoDepartment of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Atsushi NakanoDepartment of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: anakano@ucla.edu.
University of California, Los Angeles · USAlbert Einstein College of Medicine · US

Funding

UCLA MSD ProgramR25GM055052 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BARBER, PAUL HENRY, HASSON, TAMA W. · 1996 to 2021
$9.2M
Shear Stress and Light-Sheets to Study Cardiac TrabeculationR01HL129727 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HSIAI, TZUNG K, MARSDEN, ALISON L · 2015 to 2024
$3.5M
Electronica Impedance to Access Metabolically Active PlaqueR01HL118650 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HSIAI, TZUNG K · 2014 to 2022
$3.3M
Micro-Sensors to Study Electrical and Mechanical Coupling of Injured MyocardiumR01HL111437 · NHLBI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HSIAI, TZUNG K, XU, XIAOLEI · 2012 to 2020
$3.1M
Role of ABCC6 in cardivascular calcificationR01HL137241 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DEB, ARJUN · 2017 to 2020
$2.1M
Role of mesenchymal-endothelial-transition in cardiac hypertrophyR01HL129178 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DEB, ARJUN · 2015 to 2018
$1.5M
Hemogenic endocardium: contribution to the valvular tissue macrophagesR01HL127427 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI NAKANO, ATSUSHI · 2016 to 2019
$1.5M
Identifying therapeutic strategies for the multisystem genetic disorder Pseudoxanthoma ElasticumR01AR075867 · NIAMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DEB, ARJUN · 2020 to 2023
$1.4M
Howard Hughes Medical InstituteNHLBI NIH HHS R01 HL111437NHLBI NIH HHS R01 HL118650NHLBI NIH HHS R01 HL127427NHLBI NIH HHS R01 HL129178NHLBI NIH HHS R01 HL129727NHLBI NIH HHS R01 HL137241NIAMS NIH HHS R01 AR075867NIGMS NIH HHS R25 GM055052
6 · The paper itself

Abstract

During mammalian embryogenesis, de novo hematopoiesis occurs transiently in multiple anatomical sites including the yolk sac, dorsal aorta, and heart tube. A long-unanswered question is whether these local transient hematopoietic mechanisms are essential for embryonic growth. Here, we show that endocardial hematopoiesis is critical for cardiac valve remodeling as a source of tissue macrophages. Colony formation assay from explanted heart tubes and genetic lineage tracing with the endocardial specific Nfatc1-Cre mouse revealed that hemogenic endocardium is a de novo source of tissue macrophages in the endocardial cushion, the primordium of the cardiac valves. Surface marker characterization, gene expression profiling, and ex vivo phagocytosis assay revealed that the endocardially derived cardiac tissue macrophages play a phagocytic and antigen presenting role. Indeed, genetic ablation of endocardially derived macrophages caused severe valve malformation. Together, these data suggest that transient hemogenic activity in the endocardium is indispensable for the valvular tissue remodeling in the heart.

Indexed as

AnimalsEmbryo, MammalianEndocardiumGene Expression Regulation, DevelopmentalHeart ValvesHematopoiesisMacrophagesMesodermMice, TransgenicNFATC Transcription FactorsYolk SacNFATC Transcription Factorscardiac tissue macrophagecardiogenesiscongenital heart diseasehematopoiesishemogenic endocardiummultipotent cardiac progenitor cellstissue macrophagesvalve diseasevalve remodelingvalvulogenesis

Identifiers

PMID30799229
PMCPMC6440481
OpenAlexW2918073159

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.