S100A8/A9 is a valuable biomarker and treatment target to detect and modulate neutrophil involvement in myocardial infarction
(2023) In Romanian Journal of Morphology and Embryology 64(2). p.151-158- Abstract
Myocardial infarction (MI) leads to irreversible ischemic damage of the heart muscle and is the leading cause of heart failure. The ischemic cardiac injury triggers a potent local and systemic immune response. In the acute phase post-MI, neutrophils infiltrate the myocardium in large numbers and induce further cardiomyocyte death, expanding the infarcted area. The alarmin S100A8/A9 is a proinflammatory mediator primarily produced by myeloid cells, with an emerging role in MI. We previously demonstrated that short-term inhibition of S100A8/A9 during the inflammatory phase of the immune response to MI improves long-term cardiac function. In the present study, we investigated the effects of S100A8/A9 blockade on myocardial inflammation and... (More)
Myocardial infarction (MI) leads to irreversible ischemic damage of the heart muscle and is the leading cause of heart failure. The ischemic cardiac injury triggers a potent local and systemic immune response. In the acute phase post-MI, neutrophils infiltrate the myocardium in large numbers and induce further cardiomyocyte death, expanding the infarcted area. The alarmin S100A8/A9 is a proinflammatory mediator primarily produced by myeloid cells, with an emerging role in MI. We previously demonstrated that short-term inhibition of S100A8/A9 during the inflammatory phase of the immune response to MI improves long-term cardiac function. In the present study, we investigated the effects of S100A8/A9 blockade on myocardial inflammation and post-ischemic myocardial injury in a mouse model of coronary artery ligation. Immunohistochemical (IHC) staining revealed that the presence of S100A9 is strongly correlated with neutrophil infiltration in the myocardium on days 1 and 3 post-MI. A 3-day treatment with the S100A8/A9 blocker ABR-238901 starting immediately after MI decreased the number of neutrophils and S100A9 presence in the myocardium and had a positive impact on cardiac damage, reducing infarction size. These findings promote S100A9 as an IHC biomarker of neutrophil infiltration and a promising immunomodulatory target to regulate neutrophil recruitment, reduce ischemic injury and promote long-term beneficial cardiac recovery after MI.
(Less)
- author
- Mareş, Răzvan Gheorghiţă LU ; Sabău, Adrian Horaţiu ; Cocuz, Iuliu Gabriel ; Tomuţ, Mihaela Elena ; Szabo, Istvan Adorjan ; Szőke, Andreea Raluca ; Tinca, Andreea Cătălina ; Jakobsson, Gabriel LU ; Cotoi, Ovidiu Simion LU and Şchiopu, Alexandru LU
- organization
- publishing date
- 2023-04
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- infarct size, inflammation, myocardial infarction, S100A8/A9 blockade
- in
- Romanian Journal of Morphology and Embryology
- volume
- 64
- issue
- 2
- pages
- 8 pages
- publisher
- Publishing House of the Romanian Academy
- external identifiers
-
- pmid:37518871
- scopus:85166748031
- ISSN
- 1220-0522
- DOI
- 10.47162/RJME.64.2.04
- language
- English
- LU publication?
- yes
- id
- 6f7aed54-74fc-44bd-bbc7-d52b13b0ab3c
- date added to LUP
- 2023-11-03 11:24:27
- date last changed
- 2024-04-19 03:31:44
@article{6f7aed54-74fc-44bd-bbc7-d52b13b0ab3c, abstract = {{<p>Myocardial infarction (MI) leads to irreversible ischemic damage of the heart muscle and is the leading cause of heart failure. The ischemic cardiac injury triggers a potent local and systemic immune response. In the acute phase post-MI, neutrophils infiltrate the myocardium in large numbers and induce further cardiomyocyte death, expanding the infarcted area. The alarmin S100A8/A9 is a proinflammatory mediator primarily produced by myeloid cells, with an emerging role in MI. We previously demonstrated that short-term inhibition of S100A8/A9 during the inflammatory phase of the immune response to MI improves long-term cardiac function. In the present study, we investigated the effects of S100A8/A9 blockade on myocardial inflammation and post-ischemic myocardial injury in a mouse model of coronary artery ligation. Immunohistochemical (IHC) staining revealed that the presence of S100A9 is strongly correlated with neutrophil infiltration in the myocardium on days 1 and 3 post-MI. A 3-day treatment with the S100A8/A9 blocker ABR-238901 starting immediately after MI decreased the number of neutrophils and S100A9 presence in the myocardium and had a positive impact on cardiac damage, reducing infarction size. These findings promote S100A9 as an IHC biomarker of neutrophil infiltration and a promising immunomodulatory target to regulate neutrophil recruitment, reduce ischemic injury and promote long-term beneficial cardiac recovery after MI.</p>}}, author = {{Mareş, Răzvan Gheorghiţă and Sabău, Adrian Horaţiu and Cocuz, Iuliu Gabriel and Tomuţ, Mihaela Elena and Szabo, Istvan Adorjan and Szőke, Andreea Raluca and Tinca, Andreea Cătălina and Jakobsson, Gabriel and Cotoi, Ovidiu Simion and Şchiopu, Alexandru}}, issn = {{1220-0522}}, keywords = {{infarct size; inflammation; myocardial infarction; S100A8/A9 blockade}}, language = {{eng}}, number = {{2}}, pages = {{151--158}}, publisher = {{Publishing House of the Romanian Academy}}, series = {{Romanian Journal of Morphology and Embryology}}, title = {{S100A8/A9 is a valuable biomarker and treatment target to detect and modulate neutrophil involvement in myocardial infarction}}, url = {{http://dx.doi.org/10.47162/RJME.64.2.04}}, doi = {{10.47162/RJME.64.2.04}}, volume = {{64}}, year = {{2023}}, }