Abstract
Apolipoprotein (apo) B, the critical structural protein of the atherogenic lipoproteins, has two major isoforms: apoB48 and apoB100. ApoB48 is found in chylomicrons and chylomicron remnants with one apoB48 molecule per chylomicron particle. Similarly, a single apoB100 molecule is contained per particle of very-low-density lipoprotein (VLDL), intermediate density lipoprotein, LDL and lipoprotein(a). This unique one apoB per particle ratio makes plasma apoB concentration a direct measure of the number of circulating atherogenic lipoproteins. ApoB levels indicate the atherogenic particle concentration independent of the particle cholesterol content, which is variable. While LDL, the major cholesterol-carrying serum lipoprotein, is the primary therapeutic target for management and prevention of atherosclerotic cardiovascular disease, there is strong evidence that apoB is a more accurate indicator of cardiovascular risk than either total cholesterol or LDL cholesterol. This review examines multiple aspects of apoB structure and function, with a focus on the controversy over use of apoB as a therapeutic target in clinical practice. Ongoing coronary artery disease residual risk, despite lipid-lowering treatment, has left patients and clinicians with unsatisfactory options for monitoring cardiovascular health. At the present time, the substitution of apoB for LDL-C in cardiovascular disease prevention guidelines has been deemed unjustified, but discussions continue.
Highlights
Cardiovascular disease (CVD) is the leading cause of death worldwide and its prevalence is expected to continue to rise over the 15 years [1,2]
Combined with the studies showing high risk of subsequent major cardiovascular events (MCVE) despite achieving target low-density lipoprotein (LDL)-C levels, this further supports the theory that LDL cholesterol is an incomplete reflection of MCVE risk and new biomarkers may be beneficial in improving our ability to identify persons at risk for CVD and in improving outcomes for CVD patients
The risk for a coronary event increases with age, the cardiovascular risk associated with the apolipoprotein B (apoB) level decreases with age, indicating that apoB may be a better biomarker for CVD in younger patients than in older ones
Summary
Cardiovascular disease (CVD) is the leading cause of death worldwide and its prevalence is expected to continue to rise over the 15 years [1,2]. The LDL, with a long half-life of 2- to 3-days, is transported to the lysosomes where it is degraded and its lipid cargo released, while the majority of LDL receptors are recycled to the cell surface [63,64,65] In this way, apoB100 is essential in the catabolism of VLDL, LDL and IDL via its interaction with LDL receptors in the plasma. ApoB-containing lipoproteins bind to PGs via ionic interactions between the negative charged sulfate and carboxyl groups of the glycosaminoglycans (GAGs) and the positively charged basic amino acid lysine and arginine residues of the apoB100 [16,71] This binding of apoB100 to proteoglycans in the arterial wall is significant as it is considered to be the primary mechanism for the retention of LDL in the subendothelium [72]. While chylomicrons themselves are too large to penetrate the arterial wall, their remnants may do so and are thought to contribute to lipid accumulation in atherosclerotic plaque [77]
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