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Association of soluble apoptotic markers with impaired left ventricular deformation in patients with rheumatoid arthritis. Effects of inhibition of interleukin-1 activity by anakinra.
MedLine Citation:
PMID:  21947196     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Myocardial function is impaired in rheumatoid arthritis (RA). Inhibition of interleukin (IL)-1 activity reduces experimental myocardial infarction by limiting apoptosis. We investigated whether a) soluble apoptotic markers are related with impaired left ventricular (LV) performance and b) treatment with anakinra, an IL-1 receptor antagonist, reduces apoptotic markers leading to improved LV performance in RA. We studied 46 RA patients. In an acute, double-blind cross-over trial, 23 patients were randomised to a single injection of anakinra or placebo and after 48 hours (h) to the alternative treatment. In a chronic trial, 23 patients who received anakinra for 30 days were compared with 23 patients who received prednisolone. At baseline, 3 h and 30 days after treatment, we measured circulating IL-1β, tumour necrosis factor (TNF)-α, Fas, Fas-ligand and caspase-9 to assess apoptosis. At baseline and 30 days after treatment, we assessed LV longitudinal strain, strain rate and E/Em ratio using 2D-speckle tracking and tissue Doppler echocardiography. At baseline, increased apoptotic markers were related with reduced LongSRS and increased E/Em (p<0.05). After 3 h and 30 days of anakinra, there was a reduction in Fas (median 481 vs. 364 vs. 301 pg/ml), Fas-ligand (median 289 vs. 221 vs. 190 pg/ml), caspase-9 (median 1.90 vs. 1.40 vs. 1.07 ng/ml), TNF-α and IL-1β (p<0.05 for all comparisons). E/Em, LongS and LongSRS were improved after anakinra (p<0.01) and their percent changes were related with the corresponding changes of Fas and caspase-9 (p<0.05). No changes of the examined parameters were observed after prednisolone. In conclusion, inhibition of IL-1 activity by anakinra reduces apoptotic markers leading to improved LV performance in RA.
Authors:
I Ikonomidis; S Tzortzis; J Lekakis; I Paraskevaidis; P Dasou; J Parissis; M Nikolaou; S L Markantonis; P Katsimbri; G Skarantavos; I Andreadou; M Anastasiou-Nana
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-9-22
Journal Detail:
Title:  Thrombosis and haemostasis     Volume:  106     ISSN:  0340-6245     ISO Abbreviation:  -     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-9-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7608063     Medline TA:  Thromb Haemost     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Dr. Ioanna Andreadou, Department of Pharmaceutical Chemistry, University of Athens School of Pharmacy, Panepistimiopolis, 15571, Athens, Greece, E-mail: jandread@pharm.uoa.gr.
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