Matrix metalloproteinase-9 might affect adaptive immunity in non-ST segment elevation acute coronary syndromes by increasing CD31 cleavage on CD4+ T-cells
Autor: | Giovanna Liuzzo, Giulia Angelini, M Ponzo, Filippo Crea, Daniela Pedicino, Ramona Vinci, Giuseppe P Piemontese, Francesco Trotta, Domenico Galante, Luigi M. Biasucci, Davide Flego, Aureliano Ruggio |
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Rok vydání: | 2017 |
Předmět: |
CD4-Positive T-Lymphocytes
0301 basic medicine CD31 Acute coronary syndrome Down-Regulation Stimulation Adaptive Immunity 030204 cardiovascular system & hematology Flow cytometry 03 medical and health sciences 0302 clinical medicine Basic Science Downregulation and upregulation medicine Humans Prospective Studies RNA Messenger Acute Coronary Syndrome RNA Cleavage Tailored treatment medicine.diagnostic_test biology business.industry Precision medicine CD28 Acute coronary syndromes Adaptive immunity MMP-9 Cardiology and Cardiovascular Medicine Acquired immune system medicine.disease Platelet Endothelial Cell Adhesion Molecule-1 030104 developmental biology Matrix Metalloproteinase 9 Settore MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE Immunology biology.protein Antibody business Acute Coronary Syndromes |
Zdroj: | European Heart Journal |
ISSN: | 1522-9645 0195-668X |
DOI: | 10.1093/eurheartj/ehx684 |
Popis: | Aims In patients with acute coronary syndrome (ACS), the higher activity of effector T-cells suggests that mechanisms involving adaptive immunity dysregulation might play a role in coronary instability. The shedding of the functional CD31 domain 1–5 leads to uncontrolled lymphocyte activation. In experimental models, matrix metalloproteinase-9 (MMP-9) has been implicated in endothelial CD31 cleavage. Interestingly, higher serum levels of MMP-9 have been observed in ACS. We aim to investigate the mechanisms underlying CD31 dysregulation in ACS. Methods and results To assess CD31 cleavage on CD4+ T-cells, we analysed by flow cytometry CD4+ T-cells of 30 ACS, 25 stable angina (SA) patients, and 28 controls (CTRL) using two different CD31 antibodies that specifically recognize domain 1–5 or the non-functional membrane-proximal domain 6. The ratio between the domains was significantly lower in ACS than in SA and CTRL (P = 0.002 ACS vs. SA; P = 0.002 ACS vs. CTRL). After stimulation with anti-CD3/CD28, the 1–5/6 domain ratio was significantly lower in ACS than in SA (P = 0.005). ELISA of supernatants obtained from T-cell receptor-stimulated CD4+ T-cells showed higher production of MMP-9 in ACS than in SA (P |
Databáze: | OpenAIRE |
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