title: Quantitative and integrated proteome and microRNA analysis of endothelial replicative senescence.
abstract: 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.
authors.affiliation: Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Radiation Biology, Neuherberg, Germany.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Yentrapalli
authors.affiliation: Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Radiation Biology, Neuherberg, Germany.
authors.forename: Omid
authors.initials: O
authors.lastname: Azimzadeh
authors.affiliation: Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Radiation Biology, Neuherberg, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Kraemer
authors.affiliation: Institute of Pathology, Technische Universität München, Munich, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Malinowsky
authors.affiliation: Helmholtz Zentrum München, German Research Center for Environmental Health, Department of Protein Science, Proteomics Core Facility, Neuherberg, Germany.
authors.forename: Hakan
authors.initials: H
authors.lastname: Sarioglu
authors.affiliation: Institute of Pathology, Technische Universität München, Munich, Germany.
authors.forename: Karl-Friedrich
authors.initials: KF
authors.lastname: Becker
authors.affiliation: Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Radiation Biology, Neuherberg, Germany; Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Atkinson
authors.affiliation: Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Radiation Biology, Neuherberg, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Moertl
authors.affiliation: Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Radiation Biology, Neuherberg, Germany. Electronic address: soile.tapio@helmholtz-muenchen.de.
authors.forename: Soile
authors.initials: S
authors.lastname: Tapio
mesh_terms: D016922:Cellular Senescence / Q000502:physiology*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics
chemical_list: D035683:MicroRNAs; D020543:Proteome
keywords: Cellular senescence; Endothelial cell; Proteomics; miRNA