Key result
Peripheral blood mononuclear cells collected within the first 48 hours after acute myocardial infarction displayed an evolving inflammatory profile with increased P2RY11 expression (fold-change 1.72) and induced a phenotypic modification in human cardiac fibroblasts.
Why the study?
Purinergic receptors, especially P2Y11, regulate post-ischemic inflammation, but the immuno-inflammatory and P2Y11 profiles of PBMC after AMI and their impact on cardiac fibroblasts were uncharacterized.
Cohort (n=208)
No
Peripheral blood mononuclear cells display a transient reparative inflammatory profile within the first 48 hours after STEMI and can modify cardiac fibroblast phenotype in vitro, potentially participating in myocardial fibrosis.
Answers are grounded in this paper and cite their sources.
May support P2Y11 as a post-AMI inflammation target; hypothesis-generating in humans, needs prospective validation.
Pathophysiological response after acute myocardial infarction (AMI) is described as a three-stage model involving temporal phenotypic modifications of both immune cells and fibroblasts: a primary inflammatory phase, followed by a reparative phase and a fibrous scar maturation phase. Purinergic receptors, particularly the P2Y11 receptor, have been reported to be involved in the regulation of inflammation after ischemia and could act for the resolution of inflammation after AMI. For the first time, we characterized the immuno-inflammatory and P2Y11 expression profiles of peripheral blood mononuclear cells (PBMC) from AMI patients and analyzed the consequences of presenting these cells to cardiac fibroblasts in vitro. PBMC from 178 patients were collected at various times after reperfused ST-segment elevation AMI, from H0 to M12. Expression level of P2RY11 and genes involved in tolerogenic profile of dendritic cells and T cell polarization were evaluated by RT-PCR. P2Y11 protein expression was assessed by flow cytometry. PBMC and human cardiac fibroblasts (HCF) were cocultured and α-SMA/vimentin ratio was analyzed by flow cytometry. Within the first 48 h after AMI, expression levels of HMOX1, STAT3 and CD4 increased while IDO1 and TBX21/GATA3 ratio decreased. Concomitantly, the expression of P2RY11 increased in both T and B cells. In vitro, PBMC collected at H48 after AMI induced an increase in α-SMA/vimentin ratio in HCF. Our results suggest that human PBMC display an evolving inflammatory profile with reparative characteristics the first two days after AMI and secrete soluble mediators leading to the fibroblastic proteins modification, thus participating to myocardial fibrosis.
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Miquelestorena‐Standley et al. (2023) conducted a cohort in ST-segment elevation myocardial infarction (STEMI) (n=208). Acute myocardial infarction vs. Healthy donors was evaluated on P2RY11 gene expression in peripheral blood mononuclear cells within the first 48 hours (fold-change 1.72, p=0.0006). Peripheral blood mononuclear cells collected within the first 48 hours after acute myocardial infarction displayed an evolving inflammatory profile with increased P2RY11 expression (fold-change 1.72) and induced a phenotypic modification in human cardiac fibroblasts.
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