Low-density lipoprotein (LDL) (LDL)

Low-density lipoprotein (LDL) and other cholesterol-rich lipoprotein particles (such as VLDL and IDL) are macromolecular complexes that transport hydrophobic lipids, including cholesterol and triglycerides, through the bloodstream. These particles consist of a core of cholesteryl esters and triglycerides surrounded by a phospholipid monolayer containing apolipoproteins, primarily Apolipoprotein B-100 (ApoB-100). In pathological conditions like hypercholesterolemia, elevated levels of these particles lead to their accumulation and modification within the arterial wall, serving as the primary driver of atherosclerosis and cardiovascular disease. A novel therapeutic strategy targets these particles via lipid surface insertion, using amphipathic helical peptides (e.g., AEM-28) or small molecules (e.g., CVI-LM001) that insert into the lipoprotein's lipid monolayer. These agents act as artificial ligands that mimic the receptor-binding domain of Apolipoprotein E, facilitating the rapid clearance of the entire atherogenic particle from circulation via hepatic receptors like the LDL receptor (LDLR) and syndecan-1, thereby bypassing the need for endogenous apolipoprotein function.

Other names

Low-density lipoprotein (LDL)Very-low-density lipoprotein (VLDL)Apolipoprotein B-containing lipoproteinApoB-containing lipoproteinAtherogenic lipoprotein particleIntermediate-density lipoprotein (IDL)

The drug (typically an amphipathic helical peptide) inserts its hydrophobic face into the phospholipid monolayer surface of cholesterol-rich lipoprotein particles. This insertion presents a high-affinity ligand on the particle's exterior that mimics the receptor-binding domain of Apolipoprotein E, which then mediates the rapid clearance of the entire lipoprotein particle from the circulation via hepatic receptors such as the LDL receptor (LDLR) and heparan sulfate proteoglycans (e.g., syndecan-1).