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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
2...
IL-18/IL-18BP in Atherosclerosis
IL-18mRNA and Plaque Stability
mRNA expression
(relative to GAPDH)
** p < 0.0074
Symptoma...
Plasma IL-18 in Acute Coronary Syndromes
Conclusions
• IL-18 levels are related to clinical signs of
plaque instability
• ...
Inhibition of IL-18 Signaling by IL-18 Binding
Protein Transfection Prevents Development
of Atherosclerosis and Induces a ...
0
2
4
6
Empty plasmid IL-18BP plasmid
Lipid staining Area (%)
****
P < 0.0001
Empty
IL18BP
Role in Early Lesion Formation
...
Role in Advanced Lesion Composition
Empty
IL18BP
MOMA-2
0
10
20
30
40
50
60
****
P < 0.0001
Macrophage
Area(%)
0
100
200
3...
Role in Advanced Lesion Composition
Empty Plasmid IL18BP Plasmid
α-Actin
0
4
8
12
16
20
*
P < 0.05
Smoothmuscle
CellArea(%...
Role in Advanced Lesion Composition
Empty Plasmid IL18BP Plasmid
Sirius Red
0
10
20
30
40
50
60
***
P < 0.0005
Collagencon...
IL18/IL18BP Signaling in Atherosclerosis
Conclusion
Our results identify for the first time a critical role for
IL-18/IL-1...
IL18/IL18BP Signaling in Atherosclerosis
Conclusion
Our results identify for the first time a critical role for
IL-18/IL-1...
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Mallat

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Mallat

  1. 1. 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
  2. 2. IL-18/IL-18BP in Atherosclerosis IL-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
  3. 3. 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
  4. 4. 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 , France and Ares Serono, Geneva, Switzerland
  5. 5. 0 2 4 6 Empty plasmid IL-18BP plasmid Lipid staining Area (%) **** P < 0.0001 Empty IL18BP Role in Early Lesion Formation in ApoE KO Mice Lipid Staining IL18/IL18BP Signaling in Atherosclerosis
  6. 6. Role in Advanced Lesion Composition Empty IL18BP MOMA-2 0 10 20 30 40 50 60 **** P < 0.0001 Macrophage Area(%) 0 100 200 300 *** P < 0.005Tcells/mm2 IL18/IL18BP Signaling in Atherosclerosis
  7. 7. Role in Advanced Lesion Composition Empty Plasmid IL18BP Plasmid α-Actin 0 4 8 12 16 20 * P < 0.05 Smoothmuscle CellArea(%) IL18/IL18BP Signaling in Atherosclerosis
  8. 8. Role in Advanced Lesion Composition Empty Plasmid IL18BP Plasmid Sirius Red 0 10 20 30 40 50 60 *** P < 0.0005 Collagencontent(%) IL18/IL18BP Signaling in Atherosclerosis
  9. 9. 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.
  10. 10. 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.

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