Evidence map›Paper›PMID 32941598›Full record

ArticleCardiovascular research2021

Cardiac cellularity is dependent upon biological sex and is regulated by gonadal hormones.

Galen T Squiers, Micheal A McLellan, Alexei Ilinykh, Jane Branca, Nadia A Rosenthal, Alexander R Pinto

Erratum issuedOpen access · greenAbstract readComparative Study
In one paragraph

Article in Cardiovascular research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 24 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 1 pooled it
4.2field-weighted citation impact, top 4% 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

24 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.

  1. Myocardial Immune Cells: The Basis of Cardiac Immunology.Journal of immunology (Baltimore, Md. : 1950) · 2023
    Pooled it
  2. Article
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  13. Proteogenomics reveals sex-biased aging genes and coordinated splicing in cardiac aging.American journal of physiology. Heart and circulatory physiology · 2022
    Article
  14. Article
  15. Article
  16. Review
  17. Review
  18. Article
  19. Matters of the heart: Cellular sex differences.Journal of molecular and cellular cardiology · 2021
    Review
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 5 institutions in 3 countries.

Galen T SquiersDepartment of Molecular, Cellular and Developmental Biology, University of Colorado Boulder, Boulder, CO 80309, USA.ORCID 0000-0002-2490-6697
Micheal A McLellanThe Jackson Laboratory, 600 Main st, Bar Harbor, ME 04609, USA.ORCID 0000-0003-1946-5038
Alexei IlinykhAustralian Regenerative Medicine Institute, Monash University, 15 Innovation Walk, Clayton VIC 3800, Australia.ORCID 0000-0003-3351-537X
Jane BrancaThe Jackson Laboratory, 600 Main st, Bar Harbor, ME 04609, USA.
Nadia A RosenthalThe Jackson Laboratory, 600 Main st, Bar Harbor, ME 04609, USA.
Alexander R PintoBaker Heart and Diabetes Research Institute, 75 Commercial Rd, Melbourne, Victoria 3004, Australia.ORCID 0000-0001-6421-4970
Jackson Laboratory · USAustralian Regenerative Medicine Institute · AUBaker Heart and Diabetes Institute · AUTufts University · USUniversity of Colorado Boulder · US

Funding

Shared Resource ManagementP30CA034196 · NCI · JACKSON LABORATORY · PI William Carl Skarnes · 1985 to 2026
$61.9M
NCI NIH HHS P30 CA034196
6 · The paper itself

Abstract

aimsSex differences have been consistently identified in cardiac physiology and incidence of cardiac disease. However, the underlying biological causes for the differences remain unclear. We sought to characterize the cardiac non-myocyte cellular landscape in female and male hearts to determine whether cellular proportion of the heart is sex-dependent and whether endocrine factors modulate the cardiac cell proportions. METHODS AND

resultsUtilizing high-dimensional flow cytometry and immunofluorescence imaging, we found significant sex-specific differences in cellular composition of the heart in adult and juvenile mice, that develops postnatally. Removal of systemic gonadal hormones by gonadectomy results in rapid sex-specific changes in cardiac non-myocyte cellular proportions including alteration in resident mesenchymal cell and leucocyte populations, indicating gonadal hormones and their downstream targets regulate cardiac cellular composition. The ectopic reintroduction of oestrogen and testosterone to female and male mice, respectively, reverses many of these gonadectomy-induced compositional changes.

conclusionThis work shows that the constituent cell types of the mouse heart are hormone-dependent and that the cardiac cellular landscapes are distinct in females and males, remain plastic, and can be rapidly modulated by endocrine factors. These observations have implications for strategies aiming to therapeutically alter cardiac cellular heterogeneity and underscore the importance of considering biological sex for studies examining cardiac physiology and stress responses.

Indexed as

Age FactorsAnimalsCell SeparationEstradiolEstrogen Replacement TherapyFemaleFlow CytometryFluorescent Antibody TechniqueMaleMiceMice, Inbred C57BLMyocardiumOrchiectomyOvariectomyRNA-SeqSex CharacteristicsEstradiolTestosteroneCardiac cell compositionCardiac fibroblastCardiac macrophageSex differences

Identifiers

PMID32941598
PMCPMC8502469
OpenAlexW3087699863

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.