Non-HDL Cholesterol, ApoB and LDL Particle Concentration in Coronary Heart Disease Risk Prediction and Treatment

Carl E Orringer


Clin Lipidology. 2013;8(1):69-79. 

In This Article

ApoB-100 Particle Synthesis, Metabolism & Role in Atherogenesis

ApoB-100 (ApoB) is an essential component of atherogenic particles. Its synthesis in the liver is controlled by the apoB gene. The expression of this gene is not autoregulated as hepatic ApoB content is determined by proteolysis. After ApoB is synthesized it interacts with cholesteryl esters, resulting in conformational changes in ApoB, decreased degradation and increased production. Subsequent incorporation of triglycerides into this complex through the action of microsomal transfer proteins, the addition of phospholipids, and apolipoproteins E, C-I, C-II and C-III, readies the VLDL particle to be secreted into the plasma.

Following secretion, VLDL triglycerides are hydrolyzed by lipoprotein lipase and its cofactor, ApoC-II. The free fatty acids that are produced are taken up by muscle cells for energy utilization and are re-esterified to triglycerides by adipose tissue for energy storage. The remaining lipoprotein particles are VLDL remnants, of which the smallest is intermediate-density lipoprotein (IDL). Some IDL interacts with ApoE and is taken up by the LDL receptor in the liver and the remainder is hydrolyzed by hepatic lipase, resulting in the formation of LDL, the end product of VLDL catabolism. ApoA is another lipoprotein that is synthesized in the liver. It has been demonstrated to associate extracellularly with circulating ApoB lipoproteins to form lipoprotein(a) particles.[3]

Particles of VLDL, VLDL remnants, IDL, LDL and lipoprotein(a) each carry one molecule of ApoB that acts to facilitate attachment of these particles to cellular receptors.[4] Such attachment is necessary to allow LDL particles to deliver cholesteryl esters to the tissues for cell membrane formation and hormone, vitamin and bile acid synthesis. Approximately 90% of ApoB-containing particles are LDL particles, a finding that is responsible for the strong correlation between the plasma concentrations of ApoB and LDL particles.[5] This observation is strong supporting evidence for the identical recommendations for the clinical use of ApoB and LDL particle concentration (LDL-P) in initial clinical assessment and on-treatment management decisions advocated by the National Lipid Association expert panel of lipid specialists.[6]

The process of atherosclerosis is propagated by excessive plasma atherogenic particle concentration and endothelial dysfunction, resulting in the gradient-driven diffusion of ApoB-containing particles from the vascular lumen into the arterial intima. Circulating monocytes are attracted to activated endothelial cells by leukocyte adhesion molecules. These monocytes migrate into the intima where they mature into macrophages that multiply and produce proatherogenic chemokines.[7]

Proteoglycan-mediated LDL particle retention, oxidative modification and macrophage engulfment of these LDL particles result in the formation of foam cells. The ingress of smooth muscle cells promotes formation of the fibrous cap overlying these plaques. Recruitment of inflammatory cells and the expression of growth factors and additional cytokines result in thinning of the fibrous cap, setting the stage for plaque rupture, vascular thrombosis and acute coronary syndromes.[8]