National Institute for Research of Metabolic and Cardiovascular Diseases
Published January 1, 2024 | Version v1
Journal article Open

The protective role of GATA6

Creators

  • 1. Department of Chemical and Biomolecular Engineering, Johns Hopkins University Whiting School of Engineering, Baltimore, MD 21218, USA
  • 2. Present address: Naval Undersea Warfare Center, Division Newport, Newport, RI 02841, USA
  • 3. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
  • 4. W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, USA
  • 5. Institut klinicke a experimentalni mediciny
  • 6. Present address: Midland Memorial Hospital, Department of Internal Medicine, Midland, TX 79701, USA

Description

Prior research has suggested that GATA6 + pericardial macrophages may traffic to the myocardium to prevent interstitial fibrosis after myocardial infarction (MI), while subsequent literature claims that they do not. We demonstrate that GATA6 + pericardial macrophages are critical for preventing IL -33 induced pericarditis and attenuate trafficking of inflammatory monocytes and granulocytes to the pericardial cavity after MI. However, absence of GATA6 + macrophages did not affect myocardial inflammation due to MI or coxsackievirus-B3 induced myocarditis, or late -stage cardiac fibrosis and cardiac function post MI. GATA6 + macrophages are significantly less transcriptionally active following stimulation in vitro compared to bone marrow -derived macrophages and do not induce upregulation of inflammatory markers in fibroblasts. This suggests that GATA6 + pericardial macrophages attenuate inflammation through their interactions with surrounding cells. We therefore conclude that GATA6 + pericardial macrophages are critical in modulating pericardial inflammation, but do not play a significant role in controlling myocardial inflammation or fibrosis.

Notes

This work was supported by the American Heart Association (AHA) 19TPA34910007 and 20TPA35490421, the National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI) R01HL118183 and R01HL136586. T.W. was supported by the 2018 Rhett Lundy Memorial Research Fellowship from the Myocarditis Foundation. D.M.H. was fundedby the NIH/NHLBI F31HL149328.V.M. is supportedby AZV grants NU22-02-00161 and NU21-02-00402, and by the National Institute for Research of Metabolic and Cardiovascular Diseases (Program EXCELES,IDproject no. LX22NPO5104)-fundedbytheEuropeanUnion–NextGenerationEU. We would like to thank Dr. Gwendalyn Randolph of Washington University School of Medicine in St. Louis for providing GATA6fl/fl mice for these experiments. We would also like to acknowledge Xiaoling Zhang and the Johns Hopkins University Ross Flow Cytometry Core for use of their instruments for our flow cytometry experiments. The Aurora at the Ross Flow Cytometry Core is funded by NIH S10OD026859. Figures were constructed with Biorender.

Files

1-s2.0-S258900422401469X-main.pdf

Files (7.6 MB)

Name Size Download all
md5:4b8095870c5b8667f74e1bce789b036d
7.6 MB Preview Download

Additional details

Related works

Has metadata
39040070 (PMID)
Is part of
2589-0042 (ISSN)
2589-0042 (ISSN)
References
10.1016/j.isci.2024.110244 (DOI)