1. Short-term S100A8/A9 Blockade Promotes Cardiac Neovascularization after Myocardial Infarction.
- Author
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Mares RG, Suica VI, Uyy E, Boteanu RM, Ivan L, Cocuz IG, Sabau AH, Yadav V, Szabo IA, Cotoi OS, Tomut ME, Jakobsson G, Simionescu M, Antohe F, and Schiopu A
- Subjects
- Animals, Humans, Male, Time Factors, Cells, Cultured, Signal Transduction, Coronary Vessels drug effects, Coronary Vessels metabolism, Angiogenic Proteins metabolism, Angiogenesis Inducing Agents pharmacology, Myocardial Infarction metabolism, Myocardial Infarction pathology, Myocardial Infarction drug therapy, Calgranulin B metabolism, Calgranulin A metabolism, Calgranulin A genetics, Neovascularization, Physiologic drug effects, Disease Models, Animal, Human Umbilical Vein Endothelial Cells metabolism, Human Umbilical Vein Endothelial Cells drug effects, Mice, Inbred C57BL, Apoptosis drug effects, Proteomics
- 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., Competing Interests: Declarations. Ethics Approval: All institutional and national guidelines for the care and use of laboratory animals were followed and approved by the appropriate institutional committees. No human studies were carried out by the authors for this article. Conflict of Interest: The authors declare no competing interests., (© 2024. The Author(s).) more...
- Published
- 2024
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