Inhibition of interleukin-1 activity by anakinra improves endothelial coronary and aortic wall function in patients with cad and coexistent rheumatoid arthritis by reducing apoptosis and oxidative stress

Postgraduate Thesis uoadl:1317591 378 Read counter

Unit:
Κατεύθυνση Κλινική Φαρμακευτική
Library of the School of Science
Deposit date:
2013-04-05
Year:
2013
Author:
Κατσέλη Χρυσούλα
Supervisors info:
Ανδρεάδου Ιωάννα Επίκ. Καθηγήτρια ΕΚΠΑ (Επιβλέπουσα), Βαλσαμή Γεωργία Επίκ. Καθηγήτρια ΕΚΠΑ, Μαρκαντώνη-Κυρούδη Σοφία Αναπλ. Καθηγήτρια ΕΚΠΑ
Original Title:
Η αναστολή της ιντερλευκίνης-1 από το anakinra βελτιώνει την λειτουργία του στεφανιαίου ενδοθηλίου σε ασθενείς με καρδιαγγειακή νόσο και ρευματοειδή αρθρίτιδα μέσω της μείωσης του οξειδωτικού stress και της απόπτωσης
Languages:
Greek
Translated title:
Inhibition of interleukin-1 activity by anakinra improves endothelial coronary and aortic wall function in patients with cad and coexistent rheumatoid arthritis by reducing apoptosis and oxidative stress
Summary:
Background: Interleukin-1 mediates atherogenesis and coronary vasoreactivity.
Anakinra, a human recombinant interleukin-1a receptor antagonist, is used for
the treatment of rheumatoid arthritis (RA) and shows favourable effects on
endothelial and arterial function in RA patients. We investigated the effects
of anakinra on coronary endothelial and arterial function in CAD patients with
coexistent RA.
Methods: Forty patients with chronic CAD and RA (ejection fraction: 56,3 ±
16,4% ) were randomized to receive a single injection of anakinra (100mg s.c.)
or placebo and after 48 hours the alternative treatment in a double-blind
trial. 23 age and sex matched subjects with similar risk factors served as
controls. At baseline and 3 hours after treatment we assessed a) coronary flow
reserve (CFR) of the LAD using Doppler echocardiography, b) aortic strain (AS),
c) flow mediated endothelial-dependent dilation of the brachial artery (FMD) by
ultrasonography and d) Fas, Fas ligand, TNF-α, IL-1β, nitrotyrosine (NT) and
protein carbonyls (PC) serum levels. All controls had no clinical history for
CAD and a negative for ischemia treadmill exercise test.
Results: Patients had impaired FMD, CFR and AS compared to controls (p<0,001).
At baseline, NT was related with AS and FMD (r=-0,401and r=-0,386), while Fas
and FasL with CFR (r=-0,450 and r=-0,362) (p<0,05). After 3 hours of anakinra
treatment, there was an improvement in FMD, CFR and AS compared to placebo,
reaching values similar to those in controls (FMD: 5,1 ± 2,3%, vs. 13,9 ± 3,5%
vs. 8,1 ± 3,6%, p=0,006, CFR: 2,1 ± 0,7 vs. 3,0 ± 1,1 vs. 3,4 ± 0,7, p<0,001,
AS: 4,4 ± 2,3% vs. 9,6 ± 3,6% vs. 8,0 ± 2,8%, p=0,003). Furthermore, there was
a decrease in NT (median 6,66 vs. 6,15 nM/L), PC (0,131 vs. 0,091 nmol/mg
protein), Fas (51,8 vs. 49,3 pg/ml) and FasL levels (47,6 vs. 40,95 pg/ml)
after anakinra (p<0,05). There was a non significant increase in TNF-α (1,06
vs. 1,24 pg/ml) and IL-1β (3,19 vs. 3,83 pg/ml) levels. No significant changes
were observed after placebo.
Conclusion: IL-1 inhibition improves endothelial function and consequently,
coronary and aortic wall function, probably through reduction of
nitro-oxidative stress and apoptosis.
Keywords:
Interleukin-1, Rheumatoid Arthritis, Coronary Heart Disease, Anakinra, Apoptosis and Oxidative Stress
Index:
No
Number of index pages:
0
Contains images:
Yes
Number of references:
185
Number of pages:
vi, 105
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