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- December 1, 2008 |
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"Inflammation and Atherosclerosis"Dr. Peter Libby (biography)
English - 2004-06-04 - 42 minutes
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 | (49 slides) |
Summary :
In this presentation Dr. Libby presents scientific data illustrating the role of inflammation in atherosclerosis, as well as evidence for the use of biomarkers in the assessment of cardiovascular risk.
Moving away from the "rust in a pipe" analogy of atherosclerosis based on the buildup of cholesterol-containing debris in the artery, it is now understood that the artery wall is actively involved in the atherosclerotic process, in turn characterised by specific molecular signaling pathways. Inflammation plays a part not only in the initiation of atherosclerosis but also its progression, the weakening of the fibrous caps of plaques, and the enhanced thrombogenicity of plaques.
The vascular wall itself produces various inflammatory mediators including CD40 ligand (CD40L). Studies in atherosclerosis-susceptible mice have shown that interruption of CD40 signaling inhibits the formation of atherosclerotic lesions as well as the evolution of established lesions. Furthermore soluble CD40L (sCD40L) was found to be a biomarker of cardiovascular risk in apparently healthy middle-aged women and patients with acute coronary syndromes. Serum sCD40L levels were also found to be elevated in diabetic patients.
C-reactive protein, a marker of inflammation, is a predictor of cardiovascular events when measured with the high-sensitivity CRP (hs-CRP) assay. hs-CRP levels were found to add to the predictive value of the TC:HDL ratio in determining the risk of first myocardial infarction, and adds prognostic information at all levels of the Framingham risk score. CRP concentrations increase as a function of body mass index and hs-CRP levels were also found to be predictive of type 2 diabetes and incident hypertension. Unlike sCD40L, measurement of hs-CRP can be easily carried out in the clinical setting by means of a simple test, and Dr. Libby concludes his presentation with a discussion of the current AHA/CDC recommendations for the use of hs-CRP testing (to learn more about C-reactive protein and hs-CRP testing please visit this website).
Copyright © 2004 E-MedHosting.com Inc.
Learning objectives :
After viewing this presentation the participant will be able to discuss:
- Basic science data illustrating the role of inflammation in the initiation, progression and thrombotic complications of atherosclerosis
- Studies demonstrating the predictive value of biomarkers of cardiovascular risk: soluble CD40 ligand and high-sensitivity C-reactive protein (hs-CRP)
- Recommendations for hs-CRP testing from the AHA/CDC scientific statement on Markers of Inflammation and Cardiovascular Disease
Bibliographic references :
Gu L, Okada Y, Clinton SK, Gerard C, Sukhova GK, Libby P, Rollins BJ.Absence of monocyte chemoattractant protein-1 reduces atherosclerosis in low density lipoprotein receptor-deficient mice.Mol Cell. 1998 Aug;2(2):275-81.
Li H, Cybulsky MI, Gimbrone MA Jr, Libby P.An atherogenic diet rapidly induces VCAM-1, a cytokine-regulatable mononuclear leukocyte adhesion molecule, in rabbit aortic endothelium.Arterioscler Thromb. 1993 Feb;13(2):197-204.
Peter Libby, MD.Molecular Bases of the Acute Coronary Syndromes Circulation. 1995;91:2844-2850.
Peter Libby, MD; Paul M. Ridker, MD, MPH.Novel Inflammatory Markers of Coronary Risk: Theory Versus Practice Circulation. 1999;100:1148-1150.
Peter Libby, MD.Current Concepts of the Pathogenesis of the Acute Coronary Syndromes Circulation. 2001;104:365.
Libby P."Atherosclerosis: the new view."Sci Am. 2002 May;286(5):46-55.
PETER LIBBY.Inflammation in atherosclerosis Nature 2002;420:868 - 874.
Peter Libby, MD; Paul M. Ridker, MD; Attilio Maseri, MD.Inflammation and Atherosclerosis Circulation. 2002;105:1135.
François Mach, MD; Uwe Schönbeck, PhD; Jean-Yves Bonnefoy, PhD; Jordan S. Pober, MD, PhD; ; Peter Libby, MD.Activation of Monocyte/Macrophage Functions Related to Acute Atheroma Complication by Ligation of CD40-Induction of Collagenase, Stromelysin, and Tissue FactorCirculation. 1997;96:396-399.
François Mach, Uwe Schönbeck, Galina K. Sukhova, Todd Bourcier, Jean-Yves Bonnefoy, Jordan S. Pober, and Peter Libby.Functional CD40 ligand is expressed on human vascular endothelial cells, smooth muscle cells, and macrophages: Implications for CD40-CD40 ligand signaling in atherosclerosis Proc. Natl. Acad. Sci. USA. 1997;94:1931-1936.
FRANÇOIS MACH, UWE SCHÖNBECK, GALINA K. SUKHOVA, ELIZABETH ATKINSON & PETER LIBBY.Reduction of atherosclerosis in mice by inhibition of CD40 signallingNature.1998;394:200 - 203.
Thomas A. Pearson, MD, PhD (Co-Chair); George A. Mensah, MD (Co-Chair); R. Wayne Alexander, MD, PhD; Jeffrey L. Anderson, MD; Richard O. Cannon, III, MD; Michael Criqui, MD; Yazid Y. Fadl, MD; Stephen P. Fortmann, MD; Yuling Hong, MD, PhD; Gary L. Myers, PhD; Nader Rifai, PhD; Sidney C. Smith, Jr, MD; Kathryn Taubert, PhD; Russell P. Tracy, PhD; Frank Vinicor, MD Markers of Inflammation and Cardiovascular Disease Circulation. 2003;107:499.
Aruna D. Pradhan, MD,MPH; JoAnn E. Manson, MD,DrPH; Nader Rifai, PhD; Julie E. Buring, ScD; Paul M. Ridker, MD,MPH. C-Reactive Protein, Interleukin 6, and Risk of Developing Type 2 Diabetes Mellitus JAMA. 2001;286:327-334.
Tripathi Rajavashisth, Jian-Hua Qiao, Sangeetika Tripathi, Jagannath Tripathi, Nikhilesh Mishra, Michael Hua, Xu-Ping Wang, Arthur Loussararian, Steven Clinton, Peter Libby, and Aldons Lusis.Heterozygous Osteopetrotic (op) Mutation Reduces Atherosclerosis in LDL Receptor- deficient Mice JCI 1998;101(12):2702-2710.
Paul M. Ridker, MD; Robert J. Glynn, ScD; ; Charles H. Hennekens, MD C-Reactive Protein Adds to the Predictive Value of Total and HDL Cholesterol in Determining Risk of First Myocardial Infarction Circulation. 1998;97:2007-2011.
Paul M Ridker, MD; Julie E. Buring, ScD; Nancy R. Cook, ScD; Nader Rifai, PhD.C-Reactive Protein, the Metabolic Syndrome, and Risk of Incident Cardiovascular Events: An 8-Year Follow-Up of 14 719 Initially Healthy American Women Circulation. 2003;107:391.
Paul M Ridker, MD, MPH; Nancy Cook, ScD.Clinical Usefulness of Very High and Very Low Levels of C-Reactive Protein Across the Full Range of Framingham Risk Scores Circulation. 2004;109:1955-1959.
U. Schönbeck, G. K. Sukhova, K. Shimizu, F. Mach, and P. Libby.Inhibition of CD40 signaling limits evolution of established atherosclerosis in mice PNAS 2000;97(13):7458-7463.
Uwe Schönbeck, PhD*; Nerea Varo, PhD*; Peter Libby, MD; Julie Buring, ScD; Paul M. Ridker, MD.Soluble CD40L and Cardiovascular Risk in Women Circulation. 2001;104:2266.
Howard D. Sesso, ScD, MPH; Julie E. Buring, ScD; Nader Rifai, PhD; Gavin J. Blake, MD, MPH; J. Michael Gaziano, MD, MPH; Paul M. Ridker, MD, MPH. C-Reactive Protein and the Risk of Developing Hypertension JAMA. 2003;290:2945-2951.
Galina K. Sukhova, PhD; Uwe Schönbeck, PhD; Elena Rabkin, MD, PhD; Frederick J. Schoen, MD, PhD; A. Robin Poole, PhD, DSc; R. Clark Billinghurst, DVM, PhD; Peter Libby, MD.Evidence for Increased Collagenolysis by Interstitial Collagenases-1 and -3 in Vulnerable Human Atheromatous Plaques Circulation. 1999;99:2503-2509.
Nerea Varo, PhD; David Vicent, MD, PhD; Peter Libby, MD; Rebecca Nuzzo, BSc; Alfonso L. Calle-Pascual, MD, PhD; María Rosa Bernal, PhD; Arturo Fernández-Cruz, MD, PhD; Aristidis Veves, MD, DSc; Petr Jarolim, MD, PhD; Jose Javier Varo, MD, PhD; Allison Goldfine, MD; Edward Horton, MD; Uwe Schönbeck, PhD.Elevated Plasma Levels of the Atherogenic Mediator Soluble CD40 Ligand in Diabetic Patients: A Novel Target of Thiazolidinediones Circulation. 2003;107:2664.
Nerea Varo, PhD; James A. de Lemos, MD; Peter Libby, MD; David A. Morrow, MD, MPH; Sabina A. Murphy, MPH; Rebecca Nuzzo, BSc; C. Michael Gibson, MD; Christopher P. Cannon, MD; Eugene Braunwald, MD; Uwe Schönbeck, PhD.Soluble CD40L: Risk Prediction After Acute Coronary SyndromesCirculation. 2003;108:1049.
Marjolein Visser, PhD; Lex M. Bouter, PhD; Geraldine M. McQuillan, PhD; Mark H. Wener, MD; Tamara B. Harris, MD, MS. Elevated C-Reactive Protein Levels in Overweight and Obese Adults JAMA. 1999;282:2131-2135.
More information is available about C-Reactive Protein.
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