Studying the Innate Immune Response to Myocardial Infarction in a Highly Efficient Experimental Animal Model

Mareş, Răzvan Gheorghiţă; Manu, Doina; Szabó, István Adorján; Tomuţ, Mihaela Elena; Pintican, Gabriela; Cordoș, Bogdan; Jakobsson, Gabriel; Dobreanu, Minodora; Cotoi, Ovidiu Simion; Schiopu, Alexandru

doi:10.47803/rjc.2021.31.3.573

Cited by 3 publications

(2 citation statements)

References 33 publications

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“…Wild-type (C57BL/6) female mice, 8–12 weeks of age, 20–25 g body weight, underwent permanent left anterior descending (LAD) coronary artery ligation as previously described [ 20 , 21 ]. All animals were allowed to acclimatize for at least one week before being included in the study.…”

Section: Methodsmentioning

confidence: 99%

“…Mouse models of MI are essential in cardiovascular research, to assess the effects of potential treatments on cardiac function, immune cell infiltration and MI size [ 20 ]. We have previously shown that short-term S100A8/A9 blockade by ABR-238901 favorably tips the immune inflammation/repair balance in the infarcted heart and improves cardiac function long-term.…”

Section: Introductionmentioning

confidence: 99%

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S100A8/A9 is a valuable biomarker and treatment target to detect and modulate neutrophil involvement in myocardial infarction

Mareş¹,

Sabău²,

Cocuz³

et al. 2023

Rom J Morphol Embryol

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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.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

S100A8/A9 is a valuable biomarker and treatment target to detect and modulate neutrophil involvement in myocardial infarction

Mareş¹,

Sabău²,

Cocuz³

et al. 2023

Rom J Morphol Embryol

Self Cite

View full text Add to dashboard Cite

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

Mares,

Suica,

Uyy

et al. 2024

J. of Cardiovasc. Trans. Res.

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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. Graphical Abstract

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Neutrophil-to-Lymphocyte Ratio – Risk of Amputation and Mortality in Patients with Limb-Threatening Ischemia – a Systematic Review

Lăpădatu,

Russu

2024

Journal of Cardiovascular Emergencies

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Acute limb ischemia (ALI) and chronic limb-threatening ischemia (CLTI) are severe vascular conditions that can be lethal. The inflammatory response in these diseases, characterized by increased levels of neutrophils and platelets, highlights the importance of prompt management. The neutrophil-to-lymphocyte ratio (NLR) has emerged as a useful biomarker during the COVID-19 pandemic and high NLR levels were found to be associated with an increased risk of ALI and other thromboembolic events. The aim of this systematic review was to analyze the prognostic role of the NLR regarding the risk of amputation and mortality in patients diagnosed with ALI and CLTI. We included 12 studies (five for ALI, with 1,145 patients, and seven for CLTI, with 1,838 patients), following the PRISMA guidelines. Treatment results were evaluated, including amputation and mortality. We found that high NLR values were consistently associated with an increased risk of amputation and/or mortality, with pooled odds ratios ranging from 1.28 to 11.09 in patients with ALI and from 1.97 to 5.6 in patients with CLTI. The results suggest that NLR may represent an important tool for informed decision-making in the management of these patients.

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Studying the Innate Immune Response to Myocardial Infarction in a Highly Efficient Experimental Animal Model

Cited by 3 publications

References 33 publications

S100A8/A9 is a valuable biomarker and treatment target to detect and modulate neutrophil involvement in myocardial infarction

S100A8/A9 is a valuable biomarker and treatment target to detect and modulate neutrophil involvement in myocardial infarction

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

Neutrophil-to-Lymphocyte Ratio – Risk of Amputation and Mortality in Patients with Limb-Threatening Ischemia – a Systematic Review

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