Enhanced myelopoiesis and myeloid TREM1 upregulation link obesity with adverse outcomes after myocardial infarction
Abstract
Obesity induces a systemic low-grade inflammatory activation of the innate immune system potentially impairing early outcomes after myocardial infarction (MI). This study aims to analyse the impact of diet-induced obesity on myelopoiesis, myocardial inflammation, left ventricular function and survival in an experimental mouse model of MI. Male and female C57BL6/J mice were fed either a high-fat (60 kJ %) or a low-fat (10 kJ %) diet. Experimental myocardial infarction was induced after 16 weeks of feeding. Left ventricular function was studied by echocardiography. Hematopoietic progenitors and peripheral leukocytes were analysed by flow cytometry. Male obese mice exhibited notably higher body weight, significantly increased myelopoiesis in the spleen and higher leukocyte counts in peripheral blood than their female counterparts. Survival over 56 days after myocardial infarction was significantly impaired in obese compared to lean mice (58% vs. 87%). In obese mice, we found significantly elevated myocardial infarction-induced myelopoiesis in the spleen and higher granulocyte, monocyte and pro-inflammatory macrophage numbers in the myocardium. Moreover, RNA-sequencing and immunohistology revealed enhanced triggering receptor expressed on myeloid cells 1 (TREM1) expression in obese compared to lean mice on day 5 after myocardial infarction. Blockade of TREM1 led to significantly better preservation of systolic function in obese mice. After myocardial infarction, obese mice of both sexes showed enhanced myelopoiesis and impaired survival compared to lean mice. TREM1 blockade might be a promising therapeutic strategy for preserving systolic function in obese patients with myocardial infarction.
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BibTeX
@article{gladow2026enhanced,
title = {{Enhanced myelopoiesis and myeloid TREM1 upregulation link obesity with adverse outcomes after myocardial infarction}},
author = {Nadine Gladow and Ines Klohr and Xin Ding and Panagiota Arampatzi and Mugdha Srivastava and Jan Traub and Stefan Frantz and Gustavo Ramos and Ulrich Hofmann},
journal = {Basic Research in Cardiology},
year = {2026},
month = sep,
doi = {10.1007/s00395-026-01207-3},
url = {https://hal.science/hal-05780645v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Enhanced myelopoiesis and myeloid TREM1 upregulation link obesity with adverse outcomes after myocardial infarction
AU - Nadine Gladow
AU - Ines Klohr
AU - Xin Ding
AU - Panagiota Arampatzi
AU - Mugdha Srivastava
AU - Jan Traub
AU - Stefan Frantz
AU - Gustavo Ramos
AU - Ulrich Hofmann
PY - 2026
DA - 2026/09/11
JO - Basic Research in Cardiology
DO - 10.1007/s00395-026-01207-3
UR - https://hal.science/hal-05780645v1
AB - Obesity induces a systemic low-grade inflammatory activation of the innate immune system potentially impairing early outcomes after myocardial infarction (MI). This study aims to analyse the impact of diet-induced obesity on myelopoiesis, myocardial inflammation, left ventricular function and survival in an experimental mouse model of MI. Male and female C57BL6/J mice were fed either a high-fat (60 kJ %) or a low-fat (10 kJ %) diet. Experimental myocardial infarction was induced after 16 weeks of feeding. Left ventricular function was studied by echocardiography. Hematopoietic progenitors and peripheral leukocytes were analysed by flow cytometry. Male obese mice exhibited notably higher body weight, significantly increased myelopoiesis in the spleen and higher leukocyte counts in peripheral blood than their female counterparts. Survival over 56 days after myocardial infarction was significantly impaired in obese compared to lean mice (58% vs. 87%). In obese mice, we found significantly elevated myocardial infarction-induced myelopoiesis in the spleen and higher granulocyte, monocyte and pro-inflammatory macrophage numbers in the myocardium. Moreover, RNA-sequencing and immunohistology revealed enhanced triggering receptor expressed on myeloid cells 1 (TREM1) expression in obese compared to lean mice on day 5 after myocardial infarction. Blockade of TREM1 led to significantly better preservation of systolic function in obese mice. After myocardial infarction, obese mice of both sexes showed enhanced myelopoiesis and impaired survival compared to lean mice. TREM1 blockade might be a promising therapeutic strategy for preserving systolic function in obese patients with myocardial infarction.
SN - 0300-8428
SN - 1435-1803
ER -