title: Mycophenolate Mofetil and Rapamycin Induce Apoptosis in the Human Monocytic U937 Cell Line Through Two Different Pathways.
abstract: Transplant vasculopathy may be considered as an accelerated form of atherosclerosis resulting in chronic rejection of vascularized allografts. After organ transplantation, a diffuse intimal thickening is observed, leading to the development of an atherosclerosis plaque due to a significant monocyte infiltration. This results from a chronic inflammatory process induced by the immune response. In this study, we investigated the impact of two immunosuppressive drugs used in therapy initiated after organ transplantation, mycophenolate mofetil, and rapamycin, on the apoptotic response of monocytes induced or not by oxidized LDL. Here we show the pro-apoptotic effect of these two drugs through two distinct signaling pathways and we highlight a synergistic effect of rapamycin on apoptosis induced by oxidized LDL. In conclusion, since immunosuppressive therapy using mycophenolate mofetil or rapamycin can increase the cell death in a monocyte cell line, this treatment could exert similar effects on human monocytes in transplant patients, and thus, prevent transplant vasculopathy, atherosclerosis development, and chronic allograft rejection. J. Cell. Biochem. 118: 3480-3487, 2017. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Lip(Sys)2-Athérosclérose: homéostasie et trafic du cholestérol des macrophages, Univ. Paris-Sud, Université Paris-Saclay, 92290 Châtenay-Malabry, France.
authors.forename: Maxime
authors.identifier: 0000-0002-3779-3775
authors.initials: M
authors.lastname: Nowak
authors.affiliation: Lip(Sys)2-Athérosclérose: homéostasie et trafic du cholestérol des macrophages, Univ. Paris-Sud, Université Paris-Saclay, 92290 Châtenay-Malabry, France.|Ecole Pratique des Hautes Etudes, Laboratoire nutrition lipidique et apoptose dans le système vasculaire-Faculté de Pharmacie, 92290 Châtenay-Malabry, France.
authors.forename: Sylviane
authors.initials: S
authors.lastname: Tardivel
authors.affiliation: Laboratoire de Biochimie générale-AP-HP (Assistance publique-Hôpitaux de Paris)-Hôpital Necker Enfants Malades, 75015 Paris, France.
authors.forename: Thao
authors.initials: T
authors.lastname: Nguyen-Khoa
authors.affiliation: Lip(Sys)2-Chimie Analytique Pharmaceutique, Univ. Paris-Sud, Université Paris-Saclay, 92290 Châtenay-Malabry, France.
authors.forename: Sonia
authors.initials: S
authors.lastname: Abreu
authors.affiliation: Lip(Sys)2-Athérosclérose: homéostasie et trafic du cholestérol des macrophages, Univ. Paris-Sud, Université Paris-Saclay, 92290 Châtenay-Malabry, France.
authors.forename: Fatima
authors.initials: F
authors.lastname: Allaoui
authors.affiliation: Lip(Sys)2-Athérosclérose: homéostasie et trafic du cholestérol des macrophages, Univ. Paris-Sud, Université Paris-Saclay, 92290 Châtenay-Malabry, France.|Laboratoire de Biochimie-AP-HP (Assistance publique-Hôpitaux de Paris)-Hôpital Européen Georges Pompidou, 75015 Paris, France.
authors.forename: Natalie
authors.initials: N
authors.lastname: Fournier
authors.affiliation: Lip(Sys)2-Chimie Analytique Pharmaceutique, Univ. Paris-Sud, Université Paris-Saclay, 92290 Châtenay-Malabry, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Chaminade
authors.affiliation: Lip(Sys)2-Athérosclérose: homéostasie et trafic du cholestérol des macrophages, Univ. Paris-Sud, Université Paris-Saclay, 92290 Châtenay-Malabry, France.|Laboratoire de Biochimie-AP-HP (Assistance publique-Hôpitaux de Paris)-Hôpital Européen Georges Pompidou, 75015 Paris, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Paul
authors.affiliation: Lip(Sys)2-Athérosclérose: homéostasie et trafic du cholestérol des macrophages, Univ. Paris-Sud, Université Paris-Saclay, 92290 Châtenay-Malabry, France.|Ecole Pratique des Hautes Etudes, Laboratoire nutrition lipidique et apoptose dans le système vasculaire-Faculté de Pharmacie, 92290 Châtenay-Malabry, France.|Laboratoire de Biochimie générale-AP-HP (Assistance publique-Hôpitaux de Paris)-Hôpital Necker Enfants Malades, 75015 Paris, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Lacour
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology; D009000:Monocytes / Q000378:metabolism*; D009173:Mycophenolic Acid / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D020123:Sirolimus / Q000494:pharmacology*; D020298:U937 Cells
chemical_list: D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D009173:Mycophenolic Acid; D020123:Sirolimus
keywords: APOPTOSIS; ATHEROSCLEROSIS; IMMUNOSUPPRESSIVE DRUG; LIPOPROTEIN; MONOCYTE; TRANSPLANTATION