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Short-term S100A8/A9 Blockade Promotes Cardiac Neovascularization after Myocardial Infarction

Mares, Razvan Gheorghita LU ; Suica, Viorel Iulian ; Uyy, Elena ; Boteanu, Raluca Maria ; Ivan, Luminita ; Cocuz, Iuliu Gabriel ; Sabau, Adrian Horatiu ; Yadav, Vikas LU orcid ; Szabo, Istvan Adorjan LU and Cotoi, Ovidiu Simion LU , et al. (2024) In Journal of Cardiovascular Translational Research
Abstract

Acute-phase inhibition of the pro-inflammatory alarmin S100A8/A9 improves cardiac function post-myocardial infarction (MI), but the mechanisms underlying the long-term benefits of this short-term treatment remain to be elucidated. Here, we assessed the effects of S100A8/A9 blockade with the small-molecule inhibitor ABR-238901 on myocardial neovascularization in mice with induced MI. The treatment significantly reduced S100A9 and increased neovascularization in the myocardium, assessed by CD31 staining. Proteomic analysis by mass-spectrometry showed strong myocardial upregulation of the pro-angiogenic proteins filamin A (~ 10-fold) and reticulon 4 (~ 5-fold), and downregulation of the anti-angiogenic proteins Ras homolog gene family... (More)

Acute-phase inhibition of the pro-inflammatory alarmin S100A8/A9 improves cardiac function post-myocardial infarction (MI), but the mechanisms underlying the long-term benefits of this short-term treatment remain to be elucidated. Here, we assessed the effects of S100A8/A9 blockade with the small-molecule inhibitor ABR-238901 on myocardial neovascularization in mice with induced MI. The treatment significantly reduced S100A9 and increased neovascularization in the myocardium, assessed by CD31 staining. Proteomic analysis by mass-spectrometry showed strong myocardial upregulation of the pro-angiogenic proteins filamin A (~ 10-fold) and reticulon 4 (~ 5-fold), and downregulation of the anti-angiogenic proteins Ras homolog gene family member A (RhoA, ~ 4.7-fold), neutrophilic granule protein (Ngp, ~ 4.0-fold), and cathelicidin antimicrobial peptide (Camp, ~ 4.4-fold) versus controls. In-vitro, ABR-238901 protected against apoptosis induced by recombinant human S100A8/A9 in human umbilical vein endothelial cells (HUVECs). In conclusion, S100A8/A9 blockade promotes post-MI myocardial neovascularization by favorably modulating pro-angiogenic proteins in the myocardium and by inhibiting endothelial cell apoptosis.

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Contribution to journal
publication status
published
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in
Journal of Cardiovascular Translational Research
publisher
Springer
external identifiers
  • pmid:39009944
  • scopus:85198634306
ISSN
1937-5395
DOI
10.1007/s12265-024-10542-6
language
English
LU publication?
yes
additional info
© 2024. The Author(s).
id
2ee80b63-6746-4666-b070-d7d5fb8b02f5
date added to LUP
2024-10-07 08:49:06
date last changed
2025-07-16 03:26:49
@article{2ee80b63-6746-4666-b070-d7d5fb8b02f5,
  abstract     = {{<p>Acute-phase inhibition of the pro-inflammatory alarmin S100A8/A9 improves cardiac function post-myocardial infarction (MI), but the mechanisms underlying the long-term benefits of this short-term treatment remain to be elucidated. Here, we assessed the effects of S100A8/A9 blockade with the small-molecule inhibitor ABR-238901 on myocardial neovascularization in mice with induced MI. The treatment significantly reduced S100A9 and increased neovascularization in the myocardium, assessed by CD31 staining. Proteomic analysis by mass-spectrometry showed strong myocardial upregulation of the pro-angiogenic proteins filamin A (~ 10-fold) and reticulon 4 (~ 5-fold), and downregulation of the anti-angiogenic proteins Ras homolog gene family member A (RhoA, ~ 4.7-fold), neutrophilic granule protein (Ngp, ~ 4.0-fold), and cathelicidin antimicrobial peptide (Camp, ~ 4.4-fold) versus controls. In-vitro, ABR-238901 protected against apoptosis induced by recombinant human S100A8/A9 in human umbilical vein endothelial cells (HUVECs). In conclusion, S100A8/A9 blockade promotes post-MI myocardial neovascularization by favorably modulating pro-angiogenic proteins in the myocardium and by inhibiting endothelial cell apoptosis.</p>}},
  author       = {{Mares, Razvan Gheorghita and Suica, Viorel Iulian and Uyy, Elena and Boteanu, Raluca Maria and Ivan, Luminita and Cocuz, Iuliu Gabriel and Sabau, Adrian Horatiu and Yadav, Vikas and Szabo, Istvan Adorjan and Cotoi, Ovidiu Simion and Tomut, Mihaela Elena and Jakobsson, Gabriel and Simionescu, Maya and Antohe, Felicia and Schiopu, Alexandru}},
  issn         = {{1937-5395}},
  language     = {{eng}},
  month        = {{07}},
  publisher    = {{Springer}},
  series       = {{Journal of Cardiovascular Translational Research}},
  title        = {{Short-term S100A8/A9 Blockade Promotes Cardiac Neovascularization after Myocardial Infarction}},
  url          = {{http://dx.doi.org/10.1007/s12265-024-10542-6}},
  doi          = {{10.1007/s12265-024-10542-6}},
  year         = {{2024}},
}