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

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 circul...

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Published in:AGE Vol. 35; no. 4; pp. 1157 - 1172
Main Authors: Olivieri, Fabiola, Lazzarini, Raffaella, Recchioni, Rina, Marcheselli, Fiorella, Rippo, Maria Rita, Di Nuzzo, Silvia, Albertini, Maria Cristina, Graciotti, Laura, Babini, Lucia, Mariotti, Serena, Spada, Giorgio, Abbatecola, Angela Marie, Antonicelli, Roberto, Franceschi, Claudio, Procopio, Antonio Domenico
Format: Journal Article
Language:English
Published: Dordrecht Springer Netherlands 01.08.2013
Springer Nature B.V
Subjects:
Age
Aging
Biomarkers
Biomarkers - metabolism
Biomedical and Life Sciences
Cardiovascular disease
Cell Biology
Cells, Cultured
Cellular Senescence - genetics
Claudin-1 - genetics
Claudin-1 - metabolism
Coronary vessels
Endothelium, Vascular - metabolism
Endothelium, Vascular - pathology
Gene expression
Gene Expression Regulation
Genes
Genotype & phenotype
Geriatrics
Geriatrics/Gerontology
Heart failure
Heart Failure - genetics
Heart Failure - metabolism
Heart Failure - pathology
Humans
Inflammation - genetics
Inflammation - metabolism
Inflammation - pathology
Kinases
Life Sciences
Medical research
MicroRNAs
MicroRNAs - biosynthesis
MicroRNAs - genetics
Molecular Medicine
Pathology
Patients
Real-Time Polymerase Chain Reaction
Research subjects
RNA - genetics
Senescence
Signal Transduction - genetics
Statistical analysis
Studies
Telomerase
Telomere - genetics
Telomere - metabolism
Tissue Array Analysis
Tumor necrosis factor-TNF
MiR-146a
Circulating angiogenic cells
Congestive heart failure
Toll-like receptor pathway
Vascular senescence
ISSN:0161-9152, 2509-2715, 1574-4647, 1574-4647, 2509-2723
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Summary: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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ISSN:0161-9152
2509-2715
1574-4647
1574-4647
2509-2723
DOI:10.1007/s11357-012-9440-8