PMID- 30148435
OWN - NLM
STAT- Publisher
LR  - 20180827
IS  - 0392-856X (Print)
IS  - 0392-856X (Linking)
DP  - 2018 Jul 18
TI  - Methotrexate did not improve endothelial function in rheumatoid arthritis: a
      study in rats with adjuvant-induced arthritis.
AB  - OBJECTIVES: Rheumatoid arthritis is associated with an increased cardiovascular
      risk, secondary to endothelial dysfunction. There is accumulating evidence that
      methotrexate reduces cardiovascular risk in rheumatoid arthritis, but the
      mechanisms involved are still unknown. In this study, we aimed to determine the
      effect of methotrexate on endothelial function and traditional cardiovascular
      risk factors in the adjuvant-induced arthritis (AIA) rat model. METHODS: On the
      first signs of arthritis, methotrexate (1 mg/kg/week, s.c.) or saline (Vehicle)
      was administered to AIA for 3 weeks. Endothelial function was studied in aortic
      rings relaxed with acetylcholine in the presence or not of inhibitors of nitric
      oxide synthase, cyclooxygenase-2, arginase, EDHF and superoxide anions
      production. Arthritis and radiological scores, blood pressure and blood levels of
      cytokines, triglycerides, cholesterol, homocysteine and BMP-4 were measured.
      RESULTS: Although methotrexate significantly reduced the arthritis score, it had 
      no effect on Ach-induced relaxation. As regards mechanisms, methotrexate
      increased nitric oxide synthase activity and reduced the superoxide anions
      production but did not change arginase, cyclooxygenase-2 and EDHF pathways.
      Methotrexate did not change the radiological score or blood pressure, lipid,
      glucose and homocysteine levels. By contrast, methotrexate significantly reduced 
      plasma IL-1beta and TNF-alpha levels and increased serum BMP-4 level.
      CONCLUSIONS: Despite a reduction of clinical and biological inflammation,
      methotrexate did not improve endothelial function in AIA rats. Overall data
      suggest that mechanisms other than the ED reduction are likely involved, and
      remain to be elucidated to better understand the cardiovascular benefits of
      methotrexate in rheumatoid arthritis.
FAU - Bordy, Romain
AU  - Bordy R
AD  - PEPITE EA4267, FHU INCREASE, Universite Bourgogne Franche-Comte, Besancon,
      France.
FAU - Verhoeven, Frank
AU  - Verhoeven F
AD  - PEPITE EA4267, FHU INCREASE, Universite Bourgogne Franche-Comte; and Service de
      Rhumatologie, CHRU Besancon, France.
FAU - Tournier-Nappey, Maude
AU  - Tournier-Nappey M
AD  - PEPITE EA4267, FHU INCREASE, Universite Bourgogne Franche-Comte, Besancon,
      France.
FAU - Wendling, Daniel
AU  - Wendling D
AD  - Service de Rhumatologie, CHRU Besancon; and EA 4266, Universite Bourgogne
      Franche-Comte, Besancon, France.
FAU - Demougeot, Celine
AU  - Demougeot C
AD  - PEPITE EA4267, FHU INCREASE, Universite Bourgogne Franche-Comte, Besancon,
      France. cdemouge@univ-fcomte.fr.
FAU - Totoson, Perle
AU  - Totoson P
AD  - PEPITE EA4267, FHU INCREASE, Universite Bourgogne Franche-Comte, Besancon,
      France.
LA  - eng
PT  - Journal Article
DEP - 20180718
PL  - Italy
TA  - Clin Exp Rheumatol
JT  - Clinical and experimental rheumatology
JID - 8308521
EDAT- 2018/08/28 06:00
MHDA- 2018/08/28 06:00
CRDT- 2018/08/28 06:00
PHST- 2018/01/12 00:00 [received]
PHST- 2018/04/16 00:00 [accepted]
PHST- 2018/08/28 06:00 [entrez]
PHST- 2018/08/28 06:00 [pubmed]
PHST- 2018/08/28 06:00 [medline]
AID - 12603 [pii]
PST - aheadofprint
SO  - Clin Exp Rheumatol. 2018 Jul 18. pii: 12603.