Journal
ATHEROSCLEROSIS
Volume 217, Issue 2, Pages 326-330Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.atherosclerosis.2011.03.034
Keywords
Senescence; Endothelial cells; MicroRna; Microarray; Apoptosis; Cell death
Funding
- Medical Research Council, UK
- Alleanza contro il Cancro (ACC)
- MIUR [RBIP06LCA9_0023]
- AIRC [2008-2010_33-08]
- ISS [N526D5]
- Italian Human ProteomeNet [RBRN07BMCT_007]
- Telethon [GGPO4110]
- RF [73UO3, RF07EC57UO2]
- Fondazione Roma
- EFSD CRG
- MRC [MC_U132670600] Funding Source: UKRI
- Medical Research Council [MC_U132670600] Funding Source: researchfish
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Background: Increasing evidence has demonstrated that the senescence of vascular endothelial cells has critical roles in the pathogenesis of vascular dysfunction such as atherosclerosis and thrombosis. MicroRNA (miR) are small non-coding RNAs that inhibit gene expression by binding to complementary sequences in the 3'UTR of their target mRNAs. MiRs modulate a variety of biological functions such as cell development, cell differentiation, and apoptosis. Moreover, several miRs involved in endothelial cell function have been identified. Methods and results: Through a microarray approach, we have identified a miR-146a that is progressively modulated in endothelial cells with aging. In young human umbilical vein endothelial cells, this miR is involved in a premature senescence-like phenotype through direct targeting of the NOX4 protein, implicated in cell senescence and aging. Conclusions and general significance: Finding important factors that regulate endothelial cell senescence, like miR-146a, will help provide novel therapeutic strategies for vascular disorders. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
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