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 |
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| Main Authors: | , , , , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
Dordrecht
Springer Netherlands
01.08.2013
Springer Nature B.V |
| Subjects: | |
| ISSN: | 0161-9152, 2509-2715, 1574-4647, 1574-4647, 2509-2723 |
| Online Access: | Get full text |
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| Abstract | 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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| AbstractList | 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. 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 [beta]-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. [PUBLICATION ABSTRACT] 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.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. |
| Author | Rippo, Maria Rita Abbatecola, Angela Marie Franceschi, Claudio Procopio, Antonio Domenico Olivieri, Fabiola Babini, Lucia Spada, Giorgio Lazzarini, Raffaella Di Nuzzo, Silvia Graciotti, Laura Antonicelli, Roberto Mariotti, Serena Marcheselli, Fiorella Recchioni, Rina Albertini, Maria Cristina |
| Author_xml | – sequence: 1 givenname: Fabiola surname: Olivieri fullname: Olivieri, Fabiola email: f.olivieri@yhaoo.it organization: Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Center of Clinical Pathology and Innovative Therapy, IRCCS-INRCA, National Institute – sequence: 2 givenname: Raffaella surname: Lazzarini fullname: Lazzarini, Raffaella organization: Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Center of Clinical Pathology and Innovative Therapy, IRCCS-INRCA, National Institute – sequence: 3 givenname: Rina surname: Recchioni fullname: Recchioni, Rina organization: Center of Clinical Pathology and Innovative Therapy, IRCCS-INRCA, National Institute – sequence: 4 givenname: Fiorella surname: Marcheselli fullname: Marcheselli, Fiorella organization: Center of Clinical Pathology and Innovative Therapy, IRCCS-INRCA, National Institute – sequence: 5 givenname: Maria Rita surname: Rippo fullname: Rippo, Maria Rita organization: Department of Clinical and Molecular Sciences, Università Politecnica delle Marche – sequence: 6 givenname: Silvia surname: Di Nuzzo fullname: Di Nuzzo, Silvia organization: Department of Clinical and Molecular Sciences, Università Politecnica delle Marche – sequence: 7 givenname: Maria Cristina surname: Albertini fullname: Albertini, Maria Cristina organization: Dipartimento di Scienze Biomolecolari, Sezione di Biochimica e Biologia molecolare, Università degli Studi di Urbino “Carlo Bo” – sequence: 8 givenname: Laura surname: Graciotti fullname: Graciotti, Laura organization: Department of Clinical and Molecular Sciences, Università Politecnica delle Marche – sequence: 9 givenname: Lucia surname: Babini fullname: Babini, Lucia organization: Department of Clinical and Molecular Sciences, Università Politecnica delle Marche – sequence: 10 givenname: Serena surname: Mariotti fullname: Mariotti, Serena organization: Center of Clinical Pathology and Innovative Therapy, IRCCS-INRCA, National Institute – sequence: 11 givenname: Giorgio surname: Spada fullname: Spada, Giorgio organization: Dipartimento di Scienze di Base e Fondamenti, Università degli Studi di Urbino “Carlo Bo” – sequence: 12 givenname: Angela Marie surname: Abbatecola fullname: Abbatecola, Angela Marie organization: Scientific Direction, IRCCS-INRCA, National Institute – sequence: 13 givenname: Roberto surname: Antonicelli fullname: Antonicelli, Roberto organization: Cardiology Unit, IRCCS-INRCA, National Institute – sequence: 14 givenname: Claudio surname: Franceschi fullname: Franceschi, Claudio organization: Department of Experimental Pathology, “Alma Mater Studiorum” University of Bologna, Centro Interdipartimentale Galvani “CIG”, Alma Mater Studiorum University of Bologna – sequence: 15 givenname: Antonio Domenico surname: Procopio fullname: Procopio, Antonio Domenico organization: Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Center of Clinical Pathology and Innovative Therapy, IRCCS-INRCA, National Institute |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/22692818$$D View this record in MEDLINE/PubMed |
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| ContentType | Journal Article |
| Copyright | American Aging Association 2012 American Aging Association 2013 |
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| Keywords | MiR-146a Circulating angiogenic cells Congestive heart failure Toll-like receptor pathway Vascular senescence |
| Language | English |
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| PublicationSubtitle | The Official Journal of the American Aging Association |
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| Title | MiR-146a as marker of senescence-associated pro-inflammatory status in cells involved in vascular remodelling |
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