Low-density lipoprotein and very-low-density lipoprotein (LDL/VLDL)

Low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL) are essential macromolecular complexes that facilitate the transport of hydrophobic lipids, including cholesterol and triglycerides, within the bloodstream (Feingold KR, Endotext, 2024). VLDL is synthesized in the liver to transport endogenous triglycerides to peripheral tissues, where it is subsequently remodeled into LDL, the primary carrier of cholesterol to extrahepatic cells (NIH NHLBI, 2022). Pathologically, elevated levels of these lipoproteins, particularly LDL, are central to the pathogenesis of atherosclerosis, as they can penetrate the arterial intima, become oxidized, and trigger inflammatory responses leading to plaque formation (Borén J, et al., European Heart Journal, 2020). While these particles are the primary focus of cardiovascular risk management, they are typically viewed as biomarkers or metabolic products rather than direct molecular targets; pharmacological intervention usually targets the enzymes (e.g., HMG-CoA reductase) or receptors (e.g., LDL receptor) that govern their production and clearance (Sabatine MS, Nature Reviews Cardiology, 2019). Other large plasma macromolecules in this class include chylomicrons and lipoprotein(a), which also contribute to lipid transport and cardiovascular risk (StatPearls, 2023).

Other names

Apolipoprotein B-containing lipoproteinsLDLVLDLBad cholesterolBeta-lipoproteinsChylomicronsLipoprotein(a)

Therapeutic strategies focus on reducing the plasma concentration of these macromolecules by inhibiting their hepatic synthesis (e.g., MTP or ApoB inhibition), increasing their clearance from circulation by upregulating the LDL receptor (e.g., HMG-CoA reductase or PCSK9 inhibition), or physical removal via apheresis.