CoChat
Sign Up
Cited by 409Cardiac Fibrosis and RemodelingAtherosclerosis and Cardiovascular DiseasesMesenchymal stem cell research

The DOI matches its Crossref record; 143 of the 143 references it cites were found in a registry or an index.

Cardiac macrophage biology in the steady-state heart, the aging heart, and following myocardial infarction

Open access
Ma, Yonggang, Mouton, Alan J., Lindsey, Merry L.·2018·Translational Research
DOI 10.1016/j.trsl.2017.10.001PMC PMC5846093
Open this paper in CoChat — free accountOpen PDF

Abstract

Macrophages play critical roles in homeostatic maintenance of the myocardium under normal conditions and in tissue repair after injury. In the steady-state heart, resident cardiac macrophages remove senescent and dying cells and facilitate electrical conduction. In the aging heart, the shift in macrophage phenotype to a proinflammatory subtype leads to inflammaging. Following myocardial infarction (MI), macrophages recruited to the infarct produce both proinflammatory and anti-inflammatory mediators (cytokines, chemokines, matrix metalloproteinases, and growth factors), phagocytize dead cells, and promote angiogenesis and scar formation. These diverse properties are attributed to distinct macrophage subtypes and polarization status. Infarct macrophages exhibit a proinflammatory M1 phenotype early and become polarized toward an anti-inflammatory M2 phenotype later post-MI. Although this classification system is oversimplified and needs to be refined to accommodate the multiple different macrophage subtypes that have been recently identified, general concepts on macrophage roles are independent of subtype classification. This review summarizes current knowledge about cardiac macrophage origins, roles, and phenotypes in the steady state, with aging, and after MI, as well as highlights outstanding areas of investigation.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.trsl.2017.10.001

Cites

143 of 143 references verified0 citation errors · 0 not checkable

Statistics

Figures

Fig 1 Macrophage origins in the steady-state heart and the aging heart. In the steady state, the vast majority of resident cardiac macrophages originate from the yolk sac and fetal liver progenitors, with minimal dependence on blood monocytes as a source. In terms of subpopulations, CCR2+ macrophages are replenished by blood monocyte recruitment and local proliferation, whereas CCR2− macrophages are repopulated largely by local proliferation. With age, self-renewal of resident cardiac macrophage declines, and blood monocytes increasingly contribute to the cardiac macrophage population.
Fig 1 Macrophage origins in the steady-state heart and the aging heart. In the steady state, the vast majority of resident cardiac macrophages originate from the yolk sac and fetal liver progenitors, with minimal dependence on blood monocytes as a source. In terms of subpopulations, CCR2+ macrophages are replenished by blood monocyte recruitment and local proliferation, whereas CCR2− macrophages are repopulated largely by local proliferation. With age, self-renewal of resident cardiac macrophage declines, and blood monocytes increasingly contribute to the cardiac macrophage population.CC BY-NC-ND · PubMed Central
Fig 2 Macrophage origins in the postmyocardial infarction (MI) heart. Following MI, bone marrow hematopoiesis and extramedullary hematopoiesis by the spleen produce abundant numbers of monocytes, which translocate to the circulation and are recruited to the ischemic heart. In the infarct area, the vast majority of macrophages in the first 3 days are derived from recruitment of blood monocytes, and the renewal of resident macrophages is trivial; in contrast, in the nonischemic remote myocardium, macrophages arise from both local renewal of resident macrophages and recruitment of blood monocytes. The images of cells and organs were obtained from Servier Medical Art (www.servier.com).
Fig 2 Macrophage origins in the postmyocardial infarction (MI) heart. Following MI, bone marrow hematopoiesis and extramedullary hematopoiesis by the spleen produce abundant numbers of monocytes, which translocate to the circulation and are recruited to the ischemic heart. In the infarct area, the vast majority of macrophages in the first 3 days are derived from recruitment of blood monocytes, and the renewal of resident macrophages is trivial; in contrast, in the nonischemic remote myocardium, macrophages arise from both local renewal of resident macrophages and recruitment of blood monocytes. The images of cells and organs were obtained from Servier Medical Art (www.servier.com).CC BY-NC-ND · PubMed Central
Fig 3 Proposed post-MI macrophage polarization mechanisms. The integration of 2 mechanisms determines the polarization status of macrophages in the MI heart. (1) M1 and M2 macrophages originate from circulating Ly6Chigh and Ly6Clow monocytes, respectively; Recruitment of Ly6Chigh monocytes depends on CCR2 signaling, whereas recruitment of Ly6Clow monocytes is CX3CR1 dependent; and (2) the mix of pro-M1 and pro-M2 factors existing in the MI myocardium orchestrates macrophage polarization status. MI, myocardial infarction. The images of cells and organs were obtained from Servier Medical Art (www.servier.com).
Fig 3 Proposed post-MI macrophage polarization mechanisms. The integration of 2 mechanisms determines the polarization status of macrophages in the MI heart. (1) M1 and M2 macrophages originate from circulating Ly6Chigh and Ly6Clow monocytes, respectively; Recruitment of Ly6Chigh monocytes depends on CCR2 signaling, whereas recruitment of Ly6Clow monocytes is CX3CR1 dependent; and (2) the mix of pro-M1 and pro-M2 factors existing in the MI myocardium orchestrates macrophage polarization status. MI, myocardial infarction. The images of cells and organs were obtained from Servier Medical Art (www.servier.com).CC BY-NC-ND · PubMed Central

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

1 retracted

Show all 143 references

Research works printed but not linked: 1

  1. Pawelec, 1999, Immunosenescence: impact in the young as well as the old?, Mech Ageing Dev, 108, 1

Cited by

Sorted by citations

See all 409

Related

Metadata

Authors
Ma, Y., Mouton, A. J., & Lindsey, M. L.
Affiliations
University of Mississippi Medical Center (US)
Corresponding author
Lindsey, Merry L.
ORCID
Venue
Translational Research
Publisher
Elsevier BV
Published
2018-01
Volume
191
Pages
15-28
ISSN
  • 1878-1810 (ISSN-L)
  • 1931-5244
DOI
10.1016/j.trsl.2017.10.001
PMC
PMC5846093
OpenAlex
W2763341318
Cited by
405
References
143
Citations by year
2026: 34 · 2025: 27 · 2024: 64 · 2023: 73 · 2022: 49 · 2021: 50 · 2020: 55 · 2019: 32 · 2018: 21
FWCI
4.19
Type
journal article
Language
en
Open access
Licence
Locations
  • Translational research (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion, cc-by-nc-nd)
Funders
  • American Heart Association (15SDG22930009)
  • National Institutes of Health (GM104357, GM114833, HL051971, HL129823, HL075360, HL105324, GM115428)
  • Biomedical Laboratory Research and Development, VA Office of Research and Development (5I01BX000505)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
Keywords
cardiac macrophages, macrophage polarization, M1/M2 macrophages, myocardial infarction, cardiac aging, inflammaging, tissue homeostasis, phagocytosis, angiogenesis, scar formation, macrophage origin, macrophage phenotype
MeSH terms
Aging, Heart, Humans, Macrophages, Myocardial Infarction, Myocardium, Biomarkers

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review