PMID- 28152574
OWN - NLM
STAT- MEDLINE
DCOM- 20170505
LR  - 20181113
IS  - 1365-2249 (Electronic)
IS  - 0009-9104 (Print)
IS  - 0009-9104 (Linking)
VI  - 188
IP  - 2
DP  - 2017 May
TI  - Glucocorticoids improve endothelial function in rheumatoid arthritis: a study in 
      rats with adjuvant-induced arthritis.
PG  - 208-218
LID - 10.1111/cei.12938 [doi]
AB  - 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- degrees ) 
      production. Aortic expression of endothelial NOS (eNOS), Ser1177-phospho-eNOS, 
      COX-2, arginase-2, p22(phox) and p47(phox) 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- degrees  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- degrees  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)-1beta and tumour necrosis factor (TNF)-alpha 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.
CI  - (c) 2017 British Society for Immunology.
FAU - Verhoeven, F
AU  - Verhoeven F
AD  - PEPITE EA4267, FHU INCREASE, Universite Bourgogne Franche-Comte, Besancon, 
      France.
AD  - Service de Rhumatologie, CHRU Besancon, France.
FAU - Totoson, P
AU  - Totoson P
AD  - PEPITE EA4267, FHU INCREASE, Universite Bourgogne Franche-Comte, Besancon, 
      France.
FAU - Maguin-Gate, K
AU  - Maguin-Gate K
AD  - PEPITE EA4267, FHU INCREASE, Universite Bourgogne Franche-Comte, Besancon, 
      France.
FAU - Prigent-Tessier, A
AU  - Prigent-Tessier A
AD  - INSERM U1093, Universite Bourgogne Franche-Comte, Dijon, France.
FAU - Marie, C
AU  - Marie C
AD  - INSERM U1093, Universite Bourgogne Franche-Comte, Dijon, France.
FAU - Wendling, D
AU  - Wendling D
AD  - Service de Rhumatologie, CHRU Besancon, France.
AD  - EA 4266, Universite Bourgogne Franche-Comte, Besancon, France.
FAU - Moretto, J
AU  - Moretto J
AD  - PEPITE EA4267, FHU INCREASE, Universite Bourgogne Franche-Comte, Besancon, 
      France.
FAU - Prati, C
AU  - Prati C
AD  - PEPITE EA4267, FHU INCREASE, Universite Bourgogne Franche-Comte, Besancon, 
      France.
AD  - Service de Rhumatologie, CHRU Besancon, France.
FAU - Demougeot, C
AU  - Demougeot C
AD  - PEPITE EA4267, FHU INCREASE, Universite Bourgogne Franche-Comte, Besancon, 
      France.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170309
PL  - England
TA  - Clin Exp Immunol
JT  - Clinical and experimental immunology
JID - 0057202
RN  - 0 (Biological Factors)
RN  - 0 (Blood Glucose)
RN  - 0 (Cytokines)
RN  - 0 (Glucocorticoids)
RN  - 0 (Triglycerides)
RN  - 0 (endothelium-dependent hyperpolarization factor)
RN  - 11062-77-4 (Superoxides)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - 9PHQ9Y1OLM (Prednisolone)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 3.5.3.1 (Arginase)
RN  - N9YNS0M02X (Acetylcholine)
SB  - IM
MH  - Acetylcholine/pharmacology
MH  - Animals
MH  - Aorta/physiopathology
MH  - Arginase/pharmacology
MH  - Arthritis
MH  - Arthritis, Experimental/*drug therapy
MH  - Arthritis, Rheumatoid/*drug therapy/physiopathology
MH  - Biological Factors/metabolism
MH  - Blood Glucose/analysis
MH  - Blood Pressure
MH  - Cardiovascular Diseases/diagnosis
MH  - Cholesterol/blood
MH  - Cyclooxygenase 2/pharmacology
MH  - Cytokines/blood
MH  - Endothelium, Vascular/*drug effects/*physiology
MH  - Glucocorticoids/*administration & dosage
MH  - Heart Rate
MH  - Male
MH  - Prednisolone/*administration & dosage
MH  - Random Allocation
MH  - Rats
MH  - Superoxides/metabolism
MH  - Triglycerides/blood
PMC - PMC5383443
OTO - NOTNLM
OT  - adjuvant-induced arthritis
OT  - endothelial dysfunction
OT  - glucocorticoids
OT  - mechanisms
EDAT- 2017/02/06 06:00
MHDA- 2017/05/06 06:00
PMCR- 2018/05/01
CRDT- 2017/02/03 06:00
PHST- 2017/01/24 00:00 [accepted]
PHST- 2017/02/06 06:00 [pubmed]
PHST- 2017/05/06 06:00 [medline]
PHST- 2017/02/03 06:00 [entrez]
PHST- 2018/05/01 00:00 [pmc-release]
AID - CEI12938 [pii]
AID - 10.1111/cei.12938 [doi]
PST - ppublish
SO  - Clin Exp Immunol. 2017 May;188(2):208-218. doi: 10.1111/cei.12938. Epub 2017 Mar 
      9.