MiR-146a as marker of senescence-associated pro-inflammatory status in cells involved in vascular remodelling

摘要: In order to identify new markers of vascular cell senescence with potential in vivo implications, primary cultured endothelial cells, including human umbilical vein cells (HUVECs), aortic (HAECs), coronary artery (HCAECs) and ex circulating angiogenic (CACs), were analysed for microRNA (miR) expression. Among the 367 profiled miRs HUVECs, miR-146a, miR-9, miR-204 miR-367 showed highest up-regulation senescent cells. Their predicted target genes belong nine common pathways, Toll-like receptor signalling (TLR) that plays a pivotal role inflammatory response, key feature (inflammaging). MiR-146a was most up-regulated miR validation analysis (>10-fold). Mimic antagomir transfection confirmed TLR’s IL-1 receptor-associated kinase (IRAK1) protein modulation both young Significant correlations observed among miR-146a expression β-galactosidase expression, telomere length telomerase activity. hyper-expression also validated HAECs (>4-fold) HCAECs (>30-fold). We recently CACs from patients chronic heart failure (CHF) presented distinguishing senescence. Therefore, we included determination 37 CHF 35 healthy control subjects (CTR) this study. Interestingly, 1,000-fold increased compared CTR, along decreased IRAK1 protein. Moreover, significant activity observed. Overall, our findings indicate is marker senescence-associated pro-inflammatory status remodelling