Small Dense Low-Density Lipoprotein as Biomarker for Atherosclerotic Diseases

Ekaterina A Ivanova, Veronika A Myasoedova, Alexandra A Melnichenko, Andrey V Grechko, Alexander N Orekhov, Ekaterina A Ivanova, Veronika A Myasoedova, Alexandra A Melnichenko, Andrey V Grechko, Alexander N Orekhov

Abstract

Low-density lipoprotein (LDL) plays a key role in the development and progression of atherosclerosis and cardiovascular disease. LDL consists of several subclasses of particles with different sizes and densities, including large buoyant (lb) and intermediate and small dense (sd) LDLs. It has been well documented that sdLDL has a greater atherogenic potential than that of other LDL subfractions and that sdLDL cholesterol (sdLDL-C) proportion is a better marker for prediction of cardiovascular disease than that of total LDL-C. Circulating sdLDL readily undergoes multiple atherogenic modifications in blood plasma, such as desialylation, glycation, and oxidation, that further increase its atherogenicity. Modified sdLDL is a potent inductor of inflammatory processes associated with cardiovascular disease. Several laboratory methods have been developed for separation of LDL subclasses, and the results obtained by different methods can not be directly compared in most cases. Recently, the development of homogeneous assays facilitated the LDL subfraction analysis making possible large clinical studies evaluating the significance of sdLDL in the development of cardiovascular disease. Further studies are needed to establish guidelines for sdLDL evaluation and correction in clinical practice.

Figures

Figure 1
Figure 1
Hypothetical scheme of metabolic origins of LDL subclasses. Two metabolic pathways exist for the production of LDL particles from the precursors secreted by the liver. In case of low TG availability, the liver secretes mostly VLDL1 and IDL as TG-rich and TG-poor lipoprotein particles. These can be modified by LPL and HL to generate LDLI and III particles. In case of high TG availability, a distinct pattern of LDL precursors is secreted, including larger VLDL1 and VLDL2. After these modifications by LPL and HL, they give rise to LDLII and IV particles. After TG transfer to the LDL particles by CETP, they can be further delipidated by HL resulting in the formation of smaller LDL particles. TG: triglycerides; LPL: lipoprotein lipase; HL: hepatic lipase; CETP: cholesterol ester transfer protein.

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Source: PubMed

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