OBJECTIVE: Rheumatoid arthritis (RA) is associated with accelerated atherosclerosis. The reduction in cardiovascular risk that is induced by methotrexate (MTX) and anti-tumor necrosis factor α agents in RA is considered secondary to their anti-inflammatory action, but their effects on serum lipoprotein function and foam cell formation are unknown. The reduced capacity of high-density lipoprotein (HDL) to promote cell cholesterol efflux and the increased serum cell cholesterol-loading capacity (CLC) demonstrated in RA may contribute to foam cell development. The aim of this study was to investigate the influence of MTX and adalimumab treatment on serum cholesterol efflux capacity (CEC) and CLC in RA patients and to study the in vitro effects of the two drugs on macrophage cholesterol handling. METHODS: Sera from RA patients treated with MTX (n = 34) or with adalimumab and MTX (n = 22) obtained before treatment, after 6 weeks of treatment, and after 6 months of treatment were analyzed for CEC and CLC by radioisotopic and fluorometric techniques, respectively. The influence of MTX and adalimumab on macrophage cholesterol efflux and uptake was evaluated in vitro using human THP-1-derived macrophages. RESULTS: MTX treatment was associated with increases in serum HDL, low-density lipoprotein, and total cholesterol levels and with ATP-binding cassette G1-mediated and scavenger receptor class B type I (SR-BI)-mediated increases in CEC; MTX treatment was not associated with modifications in CLC. Adalimumab treatment was associated with increases in serum HDL levels, a transient increase in SR-BI-mediated CEC, a transient decrease in ATP-binding cassette A1-mediated CEC, and a significant reduction in CLC; in addition, adalimumab reduced macrophage cholesterol uptake in vitro. CONCLUSION: Antiatherosclerotic activity associated with MTX and adalimumab may be mediated by beneficial and complementary effects on lipoprotein functions and on macrophage cholesterol handling. As a whole, these mechanisms may oppose foam cell formation.
OBJECTIVE:Rheumatoid arthritis (RA) is associated with accelerated atherosclerosis. The reduction in cardiovascular risk that is induced by methotrexate (MTX) and anti-tumornecrosis factor α agents in RA is considered secondary to their anti-inflammatory action, but their effects on serum lipoprotein function and foam cell formation are unknown. The reduced capacity of high-density lipoprotein (HDL) to promote cell cholesterol efflux and the increased serum cell cholesterol-loading capacity (CLC) demonstrated in RA may contribute to foam cell development. The aim of this study was to investigate the influence of MTX and adalimumab treatment on serum cholesterol efflux capacity (CEC) and CLC in RApatients and to study the in vitro effects of the two drugs on macrophage cholesterol handling. METHODS: Sera from RApatients treated with MTX (n = 34) or with adalimumab and MTX (n = 22) obtained before treatment, after 6 weeks of treatment, and after 6 months of treatment were analyzed for CEC and CLC by radioisotopic and fluorometric techniques, respectively. The influence of MTX and adalimumab on macrophage cholesterol efflux and uptake was evaluated in vitro using humanTHP-1-derived macrophages. RESULTS:MTX treatment was associated with increases in serum HDL, low-density lipoprotein, and total cholesterol levels and with ATP-binding cassette G1-mediated and scavenger receptor class B type I (SR-BI)-mediated increases in CEC; MTX treatment was not associated with modifications in CLC. Adalimumab treatment was associated with increases in serum HDL levels, a transient increase in SR-BI-mediated CEC, a transient decrease in ATP-binding cassette A1-mediated CEC, and a significant reduction in CLC; in addition, adalimumab reduced macrophage cholesterol uptake in vitro. CONCLUSION: Antiatherosclerotic activity associated with MTX and adalimumab may be mediated by beneficial and complementary effects on lipoprotein functions and on macrophage cholesterol handling. As a whole, these mechanisms may oppose foam cell formation.
Authors: José Tuñón; Lina Badimón; Marie-Luce Bochaton-Piallat; Bertrand Cariou; Mat J Daemen; Jesus Egido; Paul C Evans; Imo E Hoefer; Daniel F J Ketelhuth; Esther Lutgens; Christian M Matter; Claudia Monaco; Sabine Steffens; Erik Stroes; Cécile Vindis; Christian Weber; Magnus Bäck Journal: Cardiovasc Res Date: 2019-01-01 Impact factor: 10.787
Authors: Dženan Mašić; Kristian Stengaard-Pedersen; Brian Bridal Løgstrup; Kim Hørslev-Petersen; Merete Lund Hetland; Peter Junker; Mikkel Østergaard; Christian Ammitzbøll; Sören Möller; Robin Christensen; Torkell Ellingsen Journal: Rheumatol Int Date: 2021-01-02 Impact factor: 2.631
Authors: Fabiola Atzeni; Javier Rodríguez-Carrio; Călin D Popa; Michael T Nurmohamed; Gabriella Szűcs; Zoltán Szekanecz Journal: Nat Rev Rheumatol Date: 2021-04-08 Impact factor: 20.543
Authors: Michelle J Ormseth; Patricia G Yancey; Joseph F Solus; S Louis Bridges; Jeffrey R Curtis; MacRae F Linton; Sergio Fazio; Sean S Davies; L Jackson Roberts; Kasey C Vickers; Valentina Kon; C Michael Stein Journal: Arthritis Rheumatol Date: 2016-09 Impact factor: 10.995