MiR-146a as marker of senescence-associated pro-inflammatory status in cells involved in vascular remodelling
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  • 作者:Fabiola Olivieri (1) (2)
    Raffaella Lazzarini (1) (2)
    Rina Recchioni (2)
    Fiorella Marcheselli (2)
    Maria Rita Rippo (1)
    Silvia Di Nuzzo (1)
    Maria Cristina Albertini (3)
    Laura Graciotti (1)
    Lucia Babini (1)
    Serena Mariotti (2)
    Giorgio Spada (4)
    Angela Marie Abbatecola (5)
    Roberto Antonicelli (6)
    Claudio Franceschi (7) (8)
    Antonio Domenico Procopio (1) (2)
  • 关键词:Vascular senescence ; MiR ; 146a ; Circulating angiogenic cells ; Congestive heart failure ; Toll ; like receptor pathway
  • 刊名:AGE
  • 出版年:2013
  • 出版时间:August 2013
  • 年:2013
  • 卷:35
  • 期:4
  • 页码:1157-1172
  • 全文大小:627KB
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  • 作者单位:Fabiola Olivieri (1) (2)
    Raffaella Lazzarini (1) (2)
    Rina Recchioni (2)
    Fiorella Marcheselli (2)
    Maria Rita Rippo (1)
    Silvia Di Nuzzo (1)
    Maria Cristina Albertini (3)
    Laura Graciotti (1)
    Lucia Babini (1)
    Serena Mariotti (2)
    Giorgio Spada (4)
    Angela Marie Abbatecola (5)
    Roberto Antonicelli (6)
    Claudio Franceschi (7) (8)
    Antonio Domenico Procopio (1) (2)

    1. Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Via Tronto 10/A, 60020, Ancona, Italy
    2. Center of Clinical Pathology and Innovative Therapy, IRCCS-INRCA, National Institute, Ancona, Italy
    3. Dipartimento di Scienze Biomolecolari, Sezione di Biochimica e Biologia molecolare, Università degli Studi di Urbino “Carlo Bo- Urbino, Italy
    4. Dipartimento di Scienze di Base e Fondamenti, Università degli Studi di Urbino “Carlo Bo- Urbino, Italy
    5. Scientific Direction, IRCCS-INRCA, National Institute, Ancona, Italy
    6. Cardiology Unit, IRCCS-INRCA, National Institute, Ancona, Italy
    7. Department of Experimental Pathology, “Alma Mater Studiorum-University of Bologna, Bologna, Italy
    8. Centro Interdipartimentale Galvani “CIG- Alma Mater Studiorum University of Bologna, Bologna, Italy
文摘
In order to identify new markers of vascular cell senescence with potential in vivo implications, primary cultured endothelial cells, including human umbilical vein endothelial cells (HUVECs), human aortic endothelial cells (HAECs), human coronary artery endothelial cells (HCAECs) and ex vivo circulating angiogenic cells (CACs), were analysed for microRNA (miR) expression. Among the 367 profiled miRs in HUVECs, miR-146a, miR-9, miR-204 and miR-367 showed the highest up-regulation in senescent cells. Their predicted target genes belong to nine common pathways, including Toll-like receptor signalling (TLR) that plays a pivotal role in inflammatory response, a key feature of senescence (inflammaging). MiR-146a was the most up-regulated miR in the validation analysis (>10-fold). Mimic and antagomir transfection confirmed TLR’s IL-1 receptor-associated kinase (IRAK1) protein modulation in both young and senescent cells. Significant correlations were observed among miR-146a expression and β-galactosidase expression, telomere length and telomerase activity. MiR-146a hyper-expression was also validated in senescent HAECs (>4-fold) and HCAECs (>30-fold). We recently showed that CACs from patients with chronic heart failure (CHF) presented a distinguishing feature of senescence. Therefore, we also included miR-146a expression determination in CACs from 37 CHF patients and 35 healthy control subjects (CTR) for this study. Interestingly, a 1,000-fold increased expression of miR-146a was observed in CACs of CHF patients compared to CTR, along with decreased expression of IRAK1 protein. Moreover, significant correlations among miR-146a expression, telomere length and telomerase activity were observed. Overall, our findings indicate that miR-146a is a marker of a senescence-associated pro-inflammatory status in vascular remodelling cells.
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