PMID- 29753231
OWN - NLM
STAT- MEDLINE
DCOM- 20191209
LR  - 20200930
IS  - 1879-1484 (Electronic)
IS  - 0021-9150 (Linking)
VI  - 274
DP  - 2018 Jul
TI  - Vascular brain-derived neurotrophic factor pathway in rats with adjuvant-induced 
      arthritis: Effect of anti-rheumatic drugs.
PG  - 77-85
LID - S0021-9150(18)30231-4 [pii]
LID - 10.1016/j.atherosclerosis.2018.05.004 [doi]
AB  - BACKGROUND AND AIMS: In rheumatoid arthritis, the control of both disease 
      activity and standard cardiovascular (CV) risk factors is expected to attenuate 
      the increased CV risk. Evidence that brain-derived neurotrophic factor (BDNF) 
      plays a role in vascular biology led us to investigate the vascular BDNF pathway 
      in arthritis rats as well as the interaction between endothelial nitric oxide 
      (NO) and BDNF production. METHODS: The aortic BDNF pathway was studied in rats 
      with adjuvant-induced arthritis, (AIA) using Western blot and immunohistochemical 
      analysis. Control of arthritis score was achieved by administration (for 3 weeks) 
      of an equipotent dosage of etanercept, prednisolone, methotrexate, celecoxib or 
      diclofenac. Aortas were exposed to an NO donor or an NO synthase inhibitor and 
      vasoreactivity experiments were performed using LM22A-4 as a TrkB agonist. 
      RESULTS: Vascular BDNF and full length tropomyosin-related kinase B receptor 
      (TrkB-FL) were higher in AIA than in control rats. These changes coincided with 
      decreased endothelial immunoreactivity in BDNF and pTrkB(tyr816) and were 
      disconnected from arthritis score. Among anti-rheumatic drugs, only prednisolone 
      and methotrexate prevented AIA-induced vascular BDNF loss. The effect of AIA on 
      aortic BDNF levels was reversed by an NO donor and reproduced by an NOS 
      inhibitor. Finally, LM22A-4 induced both NO-dependent vasodilation and 
      phosphorylation of endothelial NO synthase at serine 1177. CONCLUSIONS: Our study 
      identified changes in the BDNF/TrkB pathway as a disease activity-independent 
      component of AIA-associated changes in endothelial phenotype. It provides new 
      perspectives in the understanding and management of the high CV risk reported in 
      rheumatoid arthritis.
CI  - Copyright (c) 2018 Elsevier B.V. All rights reserved.
FAU - Pedard, Martin
AU  - Pedard M
AD  - INSERM UMR1093-CAPS, Universite Bourgogne Franche-Comte, UFR des Sciences de 
      Sante, F-21000, Dijon, France; Service de Neurologie, CHRU, Dijon, France.
FAU - Quirie, Aurore
AU  - Quirie A
AD  - INSERM UMR1093-CAPS, Universite Bourgogne Franche-Comte, UFR des Sciences de 
      Sante, F-21000, Dijon, France.
FAU - Totoson, Perle
AU  - Totoson P
AD  - EA4267 PEPITE, FHU INCREASE, Univ. Bourgogne Franche-Comte, F-25030, Besancon, 
      France.
FAU - Verhoeven, Frank
AU  - Verhoeven F
AD  - EA4267 PEPITE, FHU INCREASE, Univ. Bourgogne Franche-Comte, F-25030, Besancon, 
      France.
FAU - Garnier, Philippe
AU  - Garnier P
AD  - INSERM UMR1093-CAPS, Universite Bourgogne Franche-Comte, UFR des Sciences de 
      Sante, F-21000, Dijon, France.
FAU - Tessier, Anne
AU  - Tessier A
AD  - INSERM UMR1093-CAPS, Universite Bourgogne Franche-Comte, UFR des Sciences de 
      Sante, F-21000, Dijon, France.
FAU - Demougeot, Celine
AU  - Demougeot C
AD  - EA4267 PEPITE, FHU INCREASE, Univ. Bourgogne Franche-Comte, F-25030, Besancon, 
      France.
FAU - Marie, Christine
AU  - Marie C
AD  - INSERM UMR1093-CAPS, Universite Bourgogne Franche-Comte, UFR des Sciences de 
      Sante, F-21000, Dijon, France. Electronic address: chmarie@u-bourgogne.fr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180502
PL  - Ireland
TA  - Atherosclerosis
JT  - Atherosclerosis
JID - 0242543
RN  - 0 (Antirheumatic Agents)
RN  - 0 (Bdnf protein, rat)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cyclooxygenase Inhibitors)
RN  - 0 (Glucocorticoids)
RN  - 0 (Immunosuppressive Agents)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 9007-81-2 (Freund's Adjuvant)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 1.14.13.39 (Nos3 protein, rat)
RN  - EC 2.7.10.1 (Ntrk2 protein, rat)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
EIN - Atherosclerosis. 2019 Jan;280:201. PMID: 30301567
MH  - Animals
MH  - Antirheumatic Agents/*pharmacology
MH  - Aorta/*drug effects/metabolism
MH  - Arthritis, Experimental/chemically induced/*drug 
      therapy/metabolism/physiopathology
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Cyclooxygenase Inhibitors/pharmacology
MH  - Freund's Adjuvant
MH  - Glucocorticoids/pharmacology
MH  - Immunosuppressive Agents/pharmacology
MH  - Male
MH  - Nitric Oxide/metabolism
MH  - Nitric Oxide Synthase Type III/metabolism
MH  - Phosphorylation
MH  - Rats, Inbred Lew
MH  - Receptor, trkB/metabolism
MH  - Signal Transduction/drug effects
MH  - Vasodilation/*drug effects
OTO - NOTNLM
OT  - Adjuvant-induced arthritis
OT  - Anti-rheumatic drugs
OT  - Vascular BDNF
EDAT- 2018/05/13 06:00
MHDA- 2019/12/18 06:00
CRDT- 2018/05/13 06:00
PHST- 2017/11/27 00:00 [received]
PHST- 2018/04/11 00:00 [revised]
PHST- 2018/05/01 00:00 [accepted]
PHST- 2018/05/13 06:00 [pubmed]
PHST- 2019/12/18 06:00 [medline]
PHST- 2018/05/13 06:00 [entrez]
AID - S0021-9150(18)30231-4 [pii]
AID - 10.1016/j.atherosclerosis.2018.05.004 [doi]
PST - ppublish
SO  - Atherosclerosis. 2018 Jul;274:77-85. doi: 10.1016/j.atherosclerosis.2018.05.004. 
      Epub 2018 May 2.