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Kolodgie, et al. Heart 2004
Atherosclerosis
Risk factors: ApoB/apoA1 ratio, diabetes, abdominal obesity, smoking, hypertension, psychosocial index, fruits/veg., exercise, alcohol
dAthrosclrose Ziad Mallat, MD, PhD Department of Medicine, - - PowerPoint PPT Presentation
dAthrosclrose Ziad Mallat, MD, PhD Department of Medicine, - - PowerPoint PPT Presentation
Biologie de la Plaque dAthrosclrose Ziad Mallat, MD, PhD Department of Medicine, University of Cambridge, Cambridge, UK Inserm Atherosclerosis Kolodgie, et al. Heart 2004 Risk factors: ApoB/apoA1 ratio, diabetes, abdominal obesity,
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Hanson GK. N Engl J Med 2005
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Effect of Subendothelial Retention of Atherogenic Lipoproteins on Atherosclerosis
Skalen et al. Nature, 2002;417:750-754.
Proteoglycan- binding-defective LDL Wild type- control LDL
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Cohen JC et al. Cell Metab 2014
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Napoli et al. JCI, 1997, 100:2680-2690.
Percent of Atherogenic Sites
Composition of Atherogenic Sites in Fetal Aortas
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Charo I, NEJM 2006
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Bornfeldt KE et al. Cell Metab 2011
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Bornfeldt KE et al. Cell Metab 2011
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Weber C et al. Nat Med 2011
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Moore KJ & Tabas I. Cell 2011
Debris of dead cells (thrombogenic)
Mallat et al. 1999, 2000
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Bornfeldt KE et al. Cell Metab 2011
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Hanson GK. N Engl J Med 2005
Mallat et al. 1999, 2001 IL-10 and TGF-β
Ait-Oufella et al. 2006 nTreg and TGF-β
Mallat et al. 2003 Tr1 cells: IL-10
Herbin et al. 2012
ApoB100-Tregs
Pro-atherogenic Th1 vs atheroprotective Tregs
Clement et al., 2018
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Flego D et al.
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Klatzmann D & Abbas K, 2015
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Maintenance of tolerance
Th1 Th2 Treg Treg Mac. IL10 TGFb IFNg Treg Th2 Th1 IL10 TGFb
Stable atherosclerotic plaque Lymph node Regulation of inflammation
EC
Pathogenic immunity
- xLDL,
HSP… IFNg TLRs, IL12/IL18… IL10 TGFb IL4 IL12
Unstable atherosclerotic plaque Pathogenic Immunity
Treg Teff
Apoptotic debris Clearance
Thrombus Protective Immunity
Treg Teff
Low-dose IL2 Restablishing Healthy Balance
Low-dose IL-2 to limit plaque inflammation
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2010 Ait-Oufella et al.
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2013 Rituximab
No CD20 mAb
Large infarction Heart failure
CD20 mAb
Small infarction No heart failure
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Low Wang CC et al. Circulation 2016
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University of Cambridge British Heart Foundation Xuan LI Andy SAGE Marc CLEMENT Inserm U970 Paris, France Hafid AIT-OUFELLA JS SILVESTRE Alain TEDGUI CeMM, Medical University
- f Vienna, Austria
- CJ. BINDER
Duke University, USA Thomas F. TEDDER
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Gallego-Colon E et al. Atherosclerosis 2018
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Winkels H et al, Circ Res 2018
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Gallego-Colon E et al. Atherosclerosis 2018
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microRNA-33 Regulates Macrophage Autophagy in Atherosclerosis, Volume: 37, Issue: 6, Pages: 1058-1067, DOI: (10.1161/ATVBAHA.116.308916)
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How Common Is Residual Cholesterol/Inflammatory Risk?
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