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Apoptosis of hematopoietic progenitor-derived adipose tissue-resident macrophages contributes to insulin resistance after myocardial infarction

Vasamsetti, Sathish Babu ; Coppin, Emilie ; Zhang, Xinyi ; Florentin, Jonathan ; Koul, Sasha LU ; Götberg, Matthias LU ; Clugston, Andrew S. ; Thoma, Floyd ; Sembrat, John and Bullock, Grant C. , et al. (2020) In Science Translational Medicine 12(553).
Abstract

Patients with insulin resistance have high risk of cardiovascular disease such as myocardial infarction (MI). However, it is not known whether MI can initiate or aggravate insulin resistance. We observed that patients with ST-elevation MI and mice with MI had de novo hyperglycemia and features of insulin resistance, respectively. In mouse models of both myocardial and skeletal muscle injury, we observed that the number of visceral adipose tissue (VAT)-resident macrophages decreased because of apoptosis after these distant organ injuries. Patients displayed a similar decrease in VAT-resident macrophage numbers and developed systemic insulin resistance after ST-elevation MI. Loss of VAT-resident macrophages after MI injury led to systemic... (More)

Patients with insulin resistance have high risk of cardiovascular disease such as myocardial infarction (MI). However, it is not known whether MI can initiate or aggravate insulin resistance. We observed that patients with ST-elevation MI and mice with MI had de novo hyperglycemia and features of insulin resistance, respectively. In mouse models of both myocardial and skeletal muscle injury, we observed that the number of visceral adipose tissue (VAT)-resident macrophages decreased because of apoptosis after these distant organ injuries. Patients displayed a similar decrease in VAT-resident macrophage numbers and developed systemic insulin resistance after ST-elevation MI. Loss of VAT-resident macrophages after MI injury led to systemic insulin resistance in non-diabetic mice. Danger signaling-associated protein high mobility group box 1 was released by the dead myocardium after MI in rodents and triggered macrophage apoptosis via Toll-like receptor 4. The VAT-resident macrophage population in the steady state in mice was transcriptomically distinct from macrophages in the brain, skin, kidney, bone marrow, lungs, and liver and was derived from hematopoietic progenitor cells just after birth. Mechanistically, VAT-resident macrophage apoptosis and de novo insulin resistance in mouse models of MI were linked to diminished concentrations of macrophage colony-stimulating factor and adiponectin. Collectively, these findings demonstrate a previously unappreciated role of adipose tissue-resident macrophages in sensing remote organ injury and promoting MI pathogenesis.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Science Translational Medicine
volume
12
issue
553
article number
eaaw0638
publisher
American Association for the Advancement of Science (AAAS)
external identifiers
  • scopus:85088811710
  • pmid:32718989
ISSN
1946-6242
DOI
10.1126/scitranslmed.aaw0638
language
English
LU publication?
yes
id
0bcf820b-47e1-4ece-acb6-b3e8ea054c4c
date added to LUP
2020-08-10 09:41:18
date last changed
2024-06-13 21:12:50
@article{0bcf820b-47e1-4ece-acb6-b3e8ea054c4c,
  abstract     = {{<p>Patients with insulin resistance have high risk of cardiovascular disease such as myocardial infarction (MI). However, it is not known whether MI can initiate or aggravate insulin resistance. We observed that patients with ST-elevation MI and mice with MI had de novo hyperglycemia and features of insulin resistance, respectively. In mouse models of both myocardial and skeletal muscle injury, we observed that the number of visceral adipose tissue (VAT)-resident macrophages decreased because of apoptosis after these distant organ injuries. Patients displayed a similar decrease in VAT-resident macrophage numbers and developed systemic insulin resistance after ST-elevation MI. Loss of VAT-resident macrophages after MI injury led to systemic insulin resistance in non-diabetic mice. Danger signaling-associated protein high mobility group box 1 was released by the dead myocardium after MI in rodents and triggered macrophage apoptosis via Toll-like receptor 4. The VAT-resident macrophage population in the steady state in mice was transcriptomically distinct from macrophages in the brain, skin, kidney, bone marrow, lungs, and liver and was derived from hematopoietic progenitor cells just after birth. Mechanistically, VAT-resident macrophage apoptosis and de novo insulin resistance in mouse models of MI were linked to diminished concentrations of macrophage colony-stimulating factor and adiponectin. Collectively, these findings demonstrate a previously unappreciated role of adipose tissue-resident macrophages in sensing remote organ injury and promoting MI pathogenesis.</p>}},
  author       = {{Vasamsetti, Sathish Babu and Coppin, Emilie and Zhang, Xinyi and Florentin, Jonathan and Koul, Sasha and Götberg, Matthias and Clugston, Andrew S. and Thoma, Floyd and Sembrat, John and Bullock, Grant C. and Kostka, Dennis and St Croix, Claudette M. and Chattopadhyay, Ansuman and Rojas, Mauricio and Mulukutla, Suresh R. and Dutta, Partha}},
  issn         = {{1946-6242}},
  language     = {{eng}},
  number       = {{553}},
  publisher    = {{American Association for the Advancement of Science (AAAS)}},
  series       = {{Science Translational Medicine}},
  title        = {{Apoptosis of hematopoietic progenitor-derived adipose tissue-resident macrophages contributes to insulin resistance after myocardial infarction}},
  url          = {{http://dx.doi.org/10.1126/scitranslmed.aaw0638}},
  doi          = {{10.1126/scitranslmed.aaw0638}},
  volume       = {{12}},
  year         = {{2020}},
}