title: Different transcriptional profiling between senescent and non-senescent human coronary artery endothelial cells (HCAECs) by Omeprazole and Lansoprazole treatment.
abstract: Recent evidence suggests that high dose and/or long term use of proton pump inhibitors (PPIs) may increase the risk of adverse cardiovascular events in older patients, but mechanisms underlying these detrimental effects are not known. Taking into account that the senescent endothelial cells have been implicated in the genesis or promotion of age-related cardiovascular disease, we hypothesized an active role of PPIs in senescent cells. The aim of this study is to investigate the changes in gene expression occurring in senescent and non-senescent human coronary artery endothelial cells (HCAECs) following Omeprazole (OPZ) or Lansoprazole (LPZ) treatment. Here, we show that atherogenic response is among the most regulated processes in PPI-treated HCAECs. PPIs induced down-regulation of anti-atherogenic chemokines (CXCL11, CXCL12 and CX3CL1) in senescent but not in non-senescent cells, while the same chemokines were up-regulated in untreated senescent cells. These findings support the hypothesis that up-regulated anti-atherogenic chemokines may represent a defensive mechanism against atherosclerosis during cellular senescence, and suggest that PPIs could activate pro-atherogenic pathways by changing the secretory phenotype of senescent HCAECs. Moreover, the genes coding for fatty acid binding protein 4 (FABP4) and piezo-type mechanosensitive ion channel component 2 (PIEZO2) were modulated by PPIs treatment with respect to untreated cells. In conclusions, our results show that long-term and high dose use of PPI could change the secretory phenotype of senescent cells, suggesting one of the potential mechanisms by which use of PPI can increase adverse outcomes in older subjects.
authors.affiliation: Translational Research Ctr. of Nutrition and Ageing, Scientific and Technological Pole, IRCCS-Italian National Research Center on Aging (INRCA), Via Birarelli 8, 60121, Ancona, Italy. l.costarelli@inrca.it.
authors.forename: Laura
authors.identifier: 0000-0001-8107-9061
authors.initials: L
authors.lastname: Costarelli
authors.affiliation: Translational Research Ctr. of Nutrition and Ageing, Scientific and Technological Pole, IRCCS-Italian National Research Center on Aging (INRCA), Via Birarelli 8, 60121, Ancona, Italy.
authors.forename: Robertina
authors.initials: R
authors.lastname: Giacconi
authors.affiliation: Translational Research Ctr. of Nutrition and Ageing, Scientific and Technological Pole, IRCCS-Italian National Research Center on Aging (INRCA), Via Birarelli 8, 60121, Ancona, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Malavolta
authors.affiliation: Translational Research Ctr. of Nutrition and Ageing, Scientific and Technological Pole, IRCCS-Italian National Research Center on Aging (INRCA), Via Birarelli 8, 60121, Ancona, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Basso
authors.affiliation: Translational Research Ctr. of Nutrition and Ageing, Scientific and Technological Pole, IRCCS-Italian National Research Center on Aging (INRCA), Via Birarelli 8, 60121, Ancona, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Piacenza
authors.affiliation: Translational Research Ctr. of Nutrition and Ageing, Scientific and Technological Pole, IRCCS-Italian National Research Center on Aging (INRCA), Via Birarelli 8, 60121, Ancona, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Provinciali
authors.affiliation: Department of Clinical and Experimental Medicine, Geriatric Clinic, University of Parma and University-Hospital of Parma, Parma, Italy.
authors.forename: Marcello G
authors.initials: MG
authors.lastname: Maggio
authors.affiliation: Unit of Geriatric Pharmacoepidemiology, Research Hospital of Cosenza, Italian National Research Center on Aging (INRCA), Cosenza, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Corsonello
authors.affiliation: Italian National Research Center on Aging (INRCA), Scientific Direction, Ancona, Italy.
authors.forename: Fabrizia
authors.initials: F
authors.lastname: Lattanzio
mesh_terms: D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects / Q000502:physiology*; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D006801:Humans; D064747:Lansoprazole / Q000008:administration & dosage*; D009853:Omeprazole / Q000008:administration & dosage*; D054328:Proton Pump Inhibitors / Q000008:administration & dosage; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology; D059467:Transcriptome / Q000187:drug effects / Q000502:physiology*
chemical_list: D016207:Cytokines; D054328:Proton Pump Inhibitors; D064747:Lansoprazole; D009853:Omeprazole
keywords: Gene expression; HCAECs; Proton pump inhibitors; SASP; Senescence