Academic Journal
MicroRNA-34a Induces Vascular Smooth Muscle Cells Senescence by SIRT1 Downregulation and Promotes the Expression of Age-Associated Pro-inflammatory Secretory Factors
| العنوان: | MicroRNA-34a Induces Vascular Smooth Muscle Cells Senescence by SIRT1 Downregulation and Promotes the Expression of Age-Associated Pro-inflammatory Secretory Factors |
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| المؤلفون: | Badi, I, BURBA, ILARIA, Ruggeri, C, ZENI, FILIPPO, Bertolotti, M, Scopece, A, Pompilio, G, Raucci, A. |
| المساهمون: | Badi, I, Burba, I, Ruggeri, C, Zeni, F, Bertolotti, M, Scopece, A, Pompilio, G, Raucci, A |
| بيانات النشر: | Oxford University Press |
| سنة النشر: | 2015 |
| المجموعة: | Università degli Studi di Milano-Bicocca: BOA (Bicocca Open Archive) |
| مصطلحات موضوعية: | Inflammation, MiR-34a, SASP, SIRT1, Vascular aging |
| الوصف: | Arterial aging is a major risk factor for the occurrence of cardiovascular diseases. The aged artery is characterized by endothelial dysfunction and vascular smooth muscle cells altered physiology together with low-grade chronic inflammation. MicroRNA-34a (miR-34a) has been recently implicated in cardiac, endothelial, and endothelial progenitor cell senescence; however, its contribution to aging-associated vascular smooth muscle cells phenotype has not been explored so far. We found that miR-34a was highly expressed in aortas isolated from old mice. Moreover, its well-known target, the longevity-associated protein SIRT1, was significantly downregulated during aging in both endothelial cells and vascular smooth muscle cells. Increased miR-34a as well as decreased SIRT1 expression was also observed in replicative-senescent human aortic smooth muscle cells. miR-34a overexpression in proliferative human aortic smooth muscle cells caused cell cycle arrest along with enhanced p21 protein levels and evidence of cell senescence. Furthermore, miR-34a ectopic expression induced pro-inflammatory senescence-associated secretory phenotype molecules. Finally, SIRT1 protein significantly decreased upon miR-34a overexpression and restoration of its levels rescued miR-34a-dependent human aortic smooth muscle cells senescence, but not senescence-associated secretory phenotype factors upregulation. Taken together, our findings suggest that aging-associated increase of miR-34a expression levels, by promoting vascular smooth muscle cells senescence and inflammation through SIRT1 downregulation and senescence-associated secretory phenotype factors induction, respectively, may lead to arterial dysfunctions |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/25352462; info:eu-repo/semantics/altIdentifier/wos/WOS:000364765700002; volume:70; issue:11; firstpage:1304; lastpage:1311; numberofpages:8; journal:JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES; http://hdl.handle.net/10281/89263; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-84946616107 |
| DOI: | 10.1093/gerona/glu180 |
| الاتاحة: | http://hdl.handle.net/10281/89263 https://doi.org/10.1093/gerona/glu180 |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.E661E2A8 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/gerona/glu180 |
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