Short-term S100A8/A9 Blockade Promotes Cardiac Neovascularization after Myocardial Infarction.
J Cardiovasc Transl Res
; 2024 Jul 15.
Article
em En
| MEDLINE
| ID: mdl-39009944
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 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
J Cardiovasc Transl Res
/
J. cardiovasc. transl. res. (Online)
/
Journal of cardiovascular translational research (Online)
Assunto da revista:
ANGIOLOGIA
/
CARDIOLOGIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Romênia