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Different transcriptional profiling between senescent and non-senescent human coronary artery endothelial cells (HCAECs) by Omeprazole and Lansoprazole treatment

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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.

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Acknowledgements

This study was supported by Grant RF-2010-2312659 from the Italian Ministry of Health and Emilia Romagna Region.

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Authors and Affiliations

  1. 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

    Laura Costarelli, Robertina Giacconi, Marco Malavolta, Andrea Basso, Francesco Piacenza & Mauro Provinciali

  2. Department of Clinical and Experimental Medicine, Geriatric Clinic, University of Parma and University-Hospital of Parma, Parma, Italy

    Marcello G. Maggio

  3. Unit of Geriatric Pharmacoepidemiology, Research Hospital of Cosenza, Italian National Research Center on Aging (INRCA), Cosenza, Italy

    Andrea Corsonello

  4. Italian National Research Center on Aging (INRCA), Scientific Direction, Ancona, Italy

    Fabrizia Lattanzio

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  1. Laura Costarelli
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Correspondence to Laura Costarelli.

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Costarelli, L., Giacconi, R., Malavolta, M. et al. Different transcriptional profiling between senescent and non-senescent human coronary artery endothelial cells (HCAECs) by Omeprazole and Lansoprazole treatment. Biogerontology 18, 217–236 (2017). https://doi.org/10.1007/s10522-016-9675-3

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