092 il18 and il18 bp in atherosclerosis
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Caspase-1 p10 10 Kd hIL18R 105 Kd 75 Kd IL-18/IL-18BP in Atherosclerosis IL-18 and IL-18R in Human Carotid Plaques hIL18 25 Kd 15 Kd Atherosclerotic plaques Controls
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Transcript of 092 il18 and il18 bp in atherosclerosis
Caspase-1p10
10 Kd
hIL18R105 Kd
75 Kd
IL-18/IL-18BP in AtherosclerosisIL-18 and IL-18R in Human Carotid Plaques
hIL1825 Kd
15 Kd
Atherosclerotic plaques Controls
IL-18/IL-18BP in AtherosclerosisIL-18mRNA and Plaque Stability
mRNA expression(relative to GAPDH)
** p < 0.0074
Symptomatic Asymptomatic
1
0
2
3
4* p < 0.018
Ulcer No Ulcer
mRNA expression(relative to GAPDH)
1
0
2
3
4
Plasma IL-18 in Acute Coronary Syndromes
Conclusions
• IL-18 levels are related to clinical signs of plaque instability
• The results suggest an important role for IL-18 in ischemic myocardial dysfunction leading to severe clinical events and eventually to death
Inhibition of IL-18 Signaling by IL-18 Binding Protein Transfection Prevents Development
of Atherosclerosis and Induces a Stable Plaque Phenotype in apoE KO Mice
Mallat Z, Corbaz A, Scoazec A, Graber P, Alouani S, Esposito B, Humbert Y, Chvatchko Y, Tedgui A
INSERM U 541, IFR Circulation Paris VII, Paris , Franceand Ares Serono, Geneva, Switzerland
0
2
4
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Empty plasmid IL-18BP plasmid
Lipid staining Area (%)
****
P < 0.0001Empty
IL18BP
Role in Early Lesion Formationin ApoE KO Mice
Lipid Staining
IL18/IL18BP Signaling in Atherosclerosis
Role in Advanced Lesion Composition
Empty
IL18BP
MOMA-2
0
102030405060
****P < 0.0001
Mac
roph
age
Are
a (%
)
0
100
200
300
***
P < 0.005T
cells
/mm
2
IL18/IL18BP Signaling in Atherosclerosis
Role in Advanced Lesion Composition
Empty Plasmid IL18BP Plasmid
-Actin
0
4
8
12
16
20
*P < 0.05
Smoo
th m
uscl
eC
ell A
rea
(%)
IL18/IL18BP Signaling in Atherosclerosis
Role in Advanced Lesion Composition
Empty Plasmid IL18BP Plasmid
Sirius Red
0
10
20
30
40
50
60 ***P < 0.0005
Col
lage
n co
nten
t (%
)
IL18/IL18BP Signaling in Atherosclerosis
IL18/IL18BP Signaling in Atherosclerosis
Conclusion
Our results identify for the first time a critical role for IL-18/IL-18BP regulation in atherosclerosis and suggest a potential role for IL-18 inhibitors in reduction of plaque development/progression and promotion of plaque stability.
