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Glucocorticoids improve endothelial function in rheumatoid arthritis: a study in rats with adjuvant-induced arthritis.
Clin Exp Immunol. 2017 05; 188(2):208-218.CE

Abstract

To determine the effect of glucocorticoids (GCs) on endothelial dysfunction (ED) and on traditional cardiovascular (CV) risk factors in the adjuvant-induced arthritis (AIA) rat model. At the first signs of AIA, a high dose (HD) [10 mg/kg/day, intraperitoneally (i.p.), GC-HD] or low dose (LD) (1 mg/kg/day, i.p., GC-LD) of prednisolone was administered for 3 weeks. Endothelial function was studied in aortic rings relaxed with acetylcholine (Ach) with or without inhibitors of nitric oxide synthase (NOS), cyclooxygenase 2 (COX-2), arginase, endothelium derived hyperpolarizing factor (EDHF) and superoxide anions (O2-°) production. Aortic expression of endothelial NOS (eNOS), Ser1177-phospho-eNOS, COX-2, arginase-2, p22phox and p47phox was evaluated by Western blotting analysis. Arthritis scores, blood pressure, heart rate and blood levels of cytokines, triglycerides, cholesterol and glucose were measured. GC-HD but not GC-LD reduced arthritis score significantly and improved Ach-induced relaxation (P < 0·05). The positive effect of GC-HD resulted from increased NOS activity and EDHF production and decreased COX-2/arginase activities and O2-° production. These functional effects relied upon increased phospho-eNOS expression and decreased COX-2, arginase-2 and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase expression. Despite the lack of effect of GC-LD on ED, it increased NOS and EDHF and down-regulated O2-° pathways but did not change arginase and COX-2 pathways. GC-HD increased triglycerides levels and blood pressure significantly (P < 0·05). Both doses of GCs decreased to the same extent as plasma interleukin (IL)-1β and tumour necrosis factor (TNF)-α levels (P < 0·05). Our data demonstrated that subchronic treatment with prednisolone improved endothelial function in AIA via pleiotropic effects on endothelial pathways. These effects occurred independently of the deleterious cardiometabolic effects and the impact of prednisolone on systemic inflammation.

Authors+Show Affiliations

PEPITE EA4267, FHU INCREASE, Université Bourgogne Franche-Comté, Besançon, France. Service de Rhumatologie, CHRU Besançon, France.PEPITE EA4267, FHU INCREASE, Université Bourgogne Franche-Comté, Besançon, France.PEPITE EA4267, FHU INCREASE, Université Bourgogne Franche-Comté, Besançon, France.INSERM U1093, Université Bourgogne Franche-Comté, Dijon, France.INSERM U1093, Université Bourgogne Franche-Comté, Dijon, France.Service de Rhumatologie, CHRU Besançon, France. EA 4266, Université Bourgogne Franche-Comté, Besançon, France.PEPITE EA4267, FHU INCREASE, Université Bourgogne Franche-Comté, Besançon, France.PEPITE EA4267, FHU INCREASE, Université Bourgogne Franche-Comté, Besançon, France. Service de Rhumatologie, CHRU Besançon, France.PEPITE EA4267, FHU INCREASE, Université Bourgogne Franche-Comté, Besançon, France.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28152574

Citation

Verhoeven, F, et al. "Glucocorticoids Improve Endothelial Function in Rheumatoid Arthritis: a Study in Rats With Adjuvant-induced Arthritis." Clinical and Experimental Immunology, vol. 188, no. 2, 2017, pp. 208-218.
Verhoeven F, Totoson P, Maguin-Gaté K, et al. Glucocorticoids improve endothelial function in rheumatoid arthritis: a study in rats with adjuvant-induced arthritis. Clin Exp Immunol. 2017;188(2):208-218.
Verhoeven, F., Totoson, P., Maguin-Gaté, K., Prigent-Tessier, A., Marie, C., Wendling, D., Moretto, J., Prati, C., & Demougeot, C. (2017). Glucocorticoids improve endothelial function in rheumatoid arthritis: a study in rats with adjuvant-induced arthritis. Clinical and Experimental Immunology, 188(2), 208-218. https://doi.org/10.1111/cei.12938
Verhoeven F, et al. Glucocorticoids Improve Endothelial Function in Rheumatoid Arthritis: a Study in Rats With Adjuvant-induced Arthritis. Clin Exp Immunol. 2017;188(2):208-218. PubMed PMID: 28152574.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Glucocorticoids improve endothelial function in rheumatoid arthritis: a study in rats with adjuvant-induced arthritis. AU - Verhoeven,F, AU - Totoson,P, AU - Maguin-Gaté,K, AU - Prigent-Tessier,A, AU - Marie,C, AU - Wendling,D, AU - Moretto,J, AU - Prati,C, AU - Demougeot,C, Y1 - 2017/03/09/ PY - 2017/01/24/accepted PY - 2017/2/6/pubmed PY - 2017/5/6/medline PY - 2017/2/3/entrez KW - adjuvant-induced arthritis KW - endothelial dysfunction KW - glucocorticoids KW - mechanisms SP - 208 EP - 218 JF - Clinical and experimental immunology JO - Clin. Exp. Immunol. VL - 188 IS - 2 N2 - To determine the effect of glucocorticoids (GCs) on endothelial dysfunction (ED) and on traditional cardiovascular (CV) risk factors in the adjuvant-induced arthritis (AIA) rat model. At the first signs of AIA, a high dose (HD) [10 mg/kg/day, intraperitoneally (i.p.), GC-HD] or low dose (LD) (1 mg/kg/day, i.p., GC-LD) of prednisolone was administered for 3 weeks. Endothelial function was studied in aortic rings relaxed with acetylcholine (Ach) with or without inhibitors of nitric oxide synthase (NOS), cyclooxygenase 2 (COX-2), arginase, endothelium derived hyperpolarizing factor (EDHF) and superoxide anions (O2-°) production. Aortic expression of endothelial NOS (eNOS), Ser1177-phospho-eNOS, COX-2, arginase-2, p22phox and p47phox was evaluated by Western blotting analysis. Arthritis scores, blood pressure, heart rate and blood levels of cytokines, triglycerides, cholesterol and glucose were measured. GC-HD but not GC-LD reduced arthritis score significantly and improved Ach-induced relaxation (P < 0·05). The positive effect of GC-HD resulted from increased NOS activity and EDHF production and decreased COX-2/arginase activities and O2-° production. These functional effects relied upon increased phospho-eNOS expression and decreased COX-2, arginase-2 and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase expression. Despite the lack of effect of GC-LD on ED, it increased NOS and EDHF and down-regulated O2-° pathways but did not change arginase and COX-2 pathways. GC-HD increased triglycerides levels and blood pressure significantly (P < 0·05). Both doses of GCs decreased to the same extent as plasma interleukin (IL)-1β and tumour necrosis factor (TNF)-α levels (P < 0·05). Our data demonstrated that subchronic treatment with prednisolone improved endothelial function in AIA via pleiotropic effects on endothelial pathways. These effects occurred independently of the deleterious cardiometabolic effects and the impact of prednisolone on systemic inflammation. SN - 1365-2249 UR - https://www.unboundmedicine.com/medline/citation/28152574/Glucocorticoids_improve_endothelial_function_in_rheumatoid_arthritis:_a_study_in_rats_with_adjuvant_induced_arthritis_ L2 - https://doi.org/10.1111/cei.12938 DB - PRIME DP - Unbound Medicine ER -