Low-density lipoprotein and High-density lipoprotein particles (LDL/HDL)

Low-density lipoprotein (LDL) and High-density lipoprotein (HDL) particles are complex macromolecular assemblies composed of a hydrophobic core of cholesteryl esters and triglycerides surrounded by a shell of phospholipids, free cholesterol, and specific apolipoproteins (Feingold KR, 2024, Endotext). LDL particles primarily function to transport cholesterol from the liver to peripheral tissues; however, elevated levels are strongly associated with the development of atherosclerosis as they can become trapped and oxidized within the arterial wall (Huff T et al., 2023, StatPearls). Conversely, HDL particles facilitate reverse cholesterol transport, a process that removes excess cholesterol from peripheral cells and returns it to the liver for biliary excretion, thereby providing a cardioprotective effect (Pappan N et al., 2023, StatPearls). While these particles are the primary clinical biomarkers for cardiovascular risk, they are not single molecular targets; instead, pharmacological therapies target the enzymes, receptors, and transporters that regulate their metabolism. Common interventions include statins, which reduce LDL production, and PCSK9 inhibitors, which enhance LDL clearance from the blood. Managing the balance between these particles is a fundamental strategy in the prevention and treatment of atherosclerotic cardiovascular disease.

Other names

LipoproteinsLDL-C and HDL-CBad and Good CholesterolAtherogenic and Anti-atherogenic particlesLipoprotein complexes

Drugs modulate these particles by inhibiting endogenous cholesterol synthesis (HMG-CoA reductase inhibitors), increasing hepatic clearance via up-regulation of the LDL receptor (PCSK9 inhibitors), inhibiting intestinal cholesterol absorption (NPC1L1 inhibitors), or inhibiting the transfer of cholesteryl esters between particles (CETP inhibitors).