Lipoprotein atherogenicity: an overview of current mechanisms.
Raised serum cholesterol does not adequately explain the increased risk of CHD within populations or the relationship between diet and CHD. Nevertheless, the principal transport vehicle of cholesterol in the circulation, LDL, must still be regarded as the most atherogenic lipoprotein species, but not because of its contribution to serum cholesterol. The atherogenic potential of LDL in the majority of individuals arises from an increase in the number of small dense LDL particles and not from its cholesterol content per se. There is now a wealth of evidence from cross-sectional and prospective studies to show that LDL particle size is significantly associated with CHD and predictive of increased coronary risk. Moreover, there are a number of credible mechanisms to link small dense LDL with the atherogenic process. The rate of influx of serum lipoproteins into the arterial wall is a function of particle size, and will thus be more rapid for small dense LDL. Components of the extracellular tissue matrix in the intima, most notably proteoglycans, selectively bind small dense LDL with high affinity, sequestering this lipoprotein in a pro-oxidative environment. The oxidation of LDL promotes the final deposition of cholesterol in the arterial wall, and numerous studies have shown small dense LDL to be more susceptible to oxidative modification than its larger and lighter counterparts. An increase in the number of small dense LDL particles may originate from a defect in the metabolism of triacylglycerol-rich lipoproteins. One mechanism may involve the overproduction and increased residence time of large triacylglycerol-rich VLDL in the postprandial phase, a situation thought to arise through pathways of insulin resistance.
Griffin
B A
BA
Centre for Nutrition and Food Safety, School of Biological Sciences, University of Surrey, Guildford, UK. B.Griffin@surrey.ac.uk
D001161:Arteriosclerosis / Q000097:blood / Q000209:etiology*; D002784:Cholesterol / Q000097:blood; D003327:Coronary Disease / Q000097:blood / Q000209:etiology; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood*; D010316:Particle Size; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood
D008077:Lipoproteins, LDL; D014280:Triglycerides; D002784:Cholesterol