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- May 10, 2008 |
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"Lipoprotein Subclasses, Inflammation, and Cardiovascular Risk in the Metabolic Syndrome"Dr. Robert S. Rosenson (biography)
English - 2006-04-03 - 44 minutes
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Summary :
In this presentation Dr. Rosenson discusses data illustrating the importance of lipoprotein subclasses for cardiovascular risk prediction in individuals with the metabolic syndrome, and the relationship between lipoprotein subclasses, oxidative stress and the inflammatory response.
Which is the best predictor of CHD risk in the metabolic syndrome? According to findings from the VA-HIT study, neither the TC:HDL-C nor the ApoB:ApoA-1 ratios were significant predictors of risk however, the LDL particle:HDL particle ratio was (1). In analyses from the Framingham study, individuals with the metabolic syndrome having optimal LDL-C levels below the 20th percentile didn't all have LDL particle concentrations below the 20th percentile (2). Further, the small LDL particle concentration was found to progressively increase with the number of metabolic syndrome components whereas the concentration of large, cholesterol-rich LDL particles was found to progressively decrease; the LDL particle concentration progressively increased with increasing numbers of metabolic syndrome components, however there was no similar increase in LDL-C (3).
Dr. Rosenson talks about fasting versus postprandial lipemia and CHD risk, presenting some data on the reduction of postprandial lipemia (concentrations of triglycerides, small LDL and total LDL particles) with fenofibrate treatment in individuals with the metabolic syndrome (4), and reduction of postprandial triglycerides and oxidative stress with ciprofibrate treatment in patients with type 2 diabetes (5).
Small LDL particles pass through the endothelium more easily, and are more electronegative than large LDL particles, says Dr. Rosenson. Due to the greater binding affinity for glycosaminoglycans in the intima, these electronegative small LDL particles have a prolonged residence time in the sub-endothelial space. The metabolically active cells of the vessel wall generate free radicals which oxidize the core phospholipid on the LDL particle surface, resulting in minimally-modified oxidized LDL. Small electronegative LDL particles have a high affinity for Lp-PLA2 (lipoprotein-associated phospholipase A2) (6), and Dr. Rosenson talks about how minimally-modified oxidized LDL is acted upon by Lp-PLA2, resulting in the formation of inflammatory mediators: oxidized fatty acids and lysophosphatidylcholine, which propagate the inflammatory response.
Copyright © 2006 E-MedHosting.com Inc.
Learning objectives :
After viewing this presentation the participant will be able to discuss:
- The metabolic pathways that regulate lipoprotein metabolism in insulin resistance
- The importance of lipoprotein subclasses in cardiovascular risk assessment in individuals with the metabolic syndrome
- How changes in lipoprotein subclasses may impact on oxidative stress and elicit the inflammatory response
Bibliographic references :
1. James D. Otvos, PhD; Dorothea Collins, ScD; David S. Freedman, PhD; Irina Shalaurova, MD; Ernst J. Schaefer, MD; Judith R. McNamara, MT; Hanna E. Bloomfield, MD, MPH; Sander J. Robins, MDLow-Density Lipoprotein and High-Density Lipoprotein Particle Subclasses Predict Coronary Events and Are Favorably Changed by Gemfibrozil Therapy in the Veterans Affairs High-Density Lipoprotein Intervention Trial Circulation. 2006;113:1556-1563.
2. Schaefer EJ et al. Circulation.2004;100(Suppl III):777.
3. Sekar Kathiresan, MD; James D. Otvos, PhD; Lisa M. Sullivan, PhD; Michelle J. Keyes, MA; Ernst J. Schaefer, MD; Peter W.F. Wilson, MD; Ralph B. D’Agostino, PhD; Ramachandran S. Vasan, MD; Sander J. Robins, MDIncreased Small Low-Density Lipoprotein Particle Number: A Prominent Feature of the Metabolic Syndrome in the Framingham Heart Study Circulation. 2006;113:20-29.
4. Rosenson RS et al., Diabetes. 2005;54(Suppl 1):A239.
5. Marc Evans, MB BCh; Richard A. Anderson, MB BCh, BSc; John Graham, BSc, PhD; Gethin R. Ellis, MB BCh, BSc; Keith Morris, BSc, PhD; Stephen Davies, MB BCh, MD; Simon K. Jackson, BSc, MSc, PhD; Malcolm J. Lewis, BSc, MB BCh, MD; Michael P. Frenneaux, BSc, MD; Alan Rees, BSc, MD, MB BChCiprofibrate Therapy Improves Endothelial Function and Reduces Postprandial Lipemia and Oxidative Stress in Type 2 Diabetes Mellitus Circulation. 2000;101:1773.
6. Alexandros D. Tselepis; Christine Dentan; Sonia-Athena P. Karabina; M. John Chapman; Ewa NinioPAF-Degrading Acetylhydrolase Is Preferentially Associated With Dense LDL and VHDL-1 in Human Plasma: Catalytic Characteristics and Relation to the Monocyte-Derived Enzyme Arteriosclerosis, Thrombosis, and Vascular Biology. 1995;15:1764-1773.
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