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Yentrapalli, R. ; Azimzadeh, O. ; Kraemer, A. ; Malinowsky, K.* ; Sarioglu, H. ; Becker, K.F.* ; Atkinson, M.J. ; Mörtl, S. ; Tapio, S.

Quantitative and integrated proteome and microRNA analysis of endothelial replicative senescence.

J. Proteomics 126, 12-23 (2015)

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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.

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Age-related changes in vascular functioning are a harbinger of cardiovascular disease but the biological mechanisms during the progression of endothelial senescence have not been studied. We investigated alterations in the proteome and miRNA profiles in the course of replicative senescence using primary human umbilical vein endothelial cells as an in vitro vascular model. Quantitative proteomic profiling from early growth stage to senescence was performed by isotope-coded protein label coupled to LC-ESI-MS/MS analysis. Some proteins consistently changed their expression during the senescence whereas others appeared as deregulated only during the late senescence. The latter was accompanied by alterations in morphology of senescent endothelial cells. MicroRNA expression profiling revealed transient changes in the level of miR-16-5p, miR-28-3p and miR-886-5p in the early senescence, decrease in the level of miR-106b-3p at the late stage, and continuous changes in the expression of miR-181a-5p and miR-376a-3p during the whole senescence process. Integrating data on proteomic and microRNA changes indicated potential crosstalk between specific proteins and non-coding RNAs in the regulation of metabolism, cell cycle progression and cytoskeletal organization in the endothelial senescence. The knowledge of molecular targets that change during the senescence can ultimately contribute to a better understanding and prevention of age-related vascular diseases. SIGNIFICANCE: Endothelial cell senescence has been associated to age-related cardiovascular disease. Although replicative senescence was discovered more than 50years ago, detailed molecular mechanisms behind this phenomenon remain to be elucidated. This study describes detailed proteome and miRNAome analyses in the progressing senescence of human umbilical vein endothelial cells. The in silico integration of the two data sets indicated the important role of miRNAs in the regulation of cell cycle progression, adhesion and metabolic alteration in the cellular aging. This study adds to our knowledge of age-induced vascular alterations and contributes to our understanding and prevention of age-related vascular diseases.

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