Immuno-inflammatory response in patients after myocardial infarction and involvement in fibrosis in vitro

Abstract Background Pathophysiology of acute myocardial infarction (AMI) has been described in mice and is based on a three-stage model involving temporal modifications immune cells fibroblasts. The inflammatory phase followed by reparative fibrous scar maturation phase. Purinergic signaling, particularly P2Y11 receptor, reported to be involved the regulation inflammation after ischemia could an actor resolution AMI. Purpose aims our study were: (1) characterize P2Y11R profiles AMI patients (2) analyze interactions between patients' cardiac fibroblasts vitro. Methods We collected peripheral blood mononuclear (PBMC) 182 at various times (H0, H4, H24, H48, D3, M1, M6, M12) reperfused ST-segment elevation AMI, 30 healthy donors. Expression level genes tolerogenicity profile dendritic (HMOX1, STAT3, IDO1), T cell polarization (CD4, FOXP3, TBX21/GATA3) as well P2RY11 were evaluated RT-PCR. expression was analyzed using flow cytometry. PBMC human (HCF) co-cultured during one day (5PBMC/1 HCF) gene (ACTA2/VIM, COL1A1), phenotype (α-SMA/vimentin) secretory (soluble collagen) RT-PCR, cytometry Sircol assay. Results In first 48 hours HMOX1 (fold-change = 8.478 p<0.0001), STAT3 (2.856 H0, p=0.0027) CD4 increased (2.451 p=0.0052); IDO1 (0.2055 p<0.0001) TBX21/GATA3 ratio decreased (0.4498 p=0.0026); FOXP3 did not vary significantly. same time, (2.124 p=0.0015) protein (median MFI 845.5 H0 vs 229.5 for donors, p=0.0375). vitro, we observed non-significant increase ACTA2/VIM HCF with M6 PBMC; α-SMA/vimentin M12 COL1A1 soluble collagen coculture supernatant M1 PBMC. Conclusion Our results suggest that evolution response that, 2 days, circulating have participate transformation fibroblast into myofibroblasts. Funding Acknowledgement Type funding sources: Foundation. Main source(s): Fondation pour la recherche médicale