Phosphatidylcholine (on High-Density Lipoprotein particles) (PC (on HDL))

Phosphatidylcholine (PC) is the predominant phospholipid found on the surface of high-density lipoprotein (HDL) particles, where it serves both structural and functional roles. Biologically, it acts as the essential acyl donor for the enzyme lecithin-cholesterol acyltransferase (LCAT), which converts free cholesterol into cholesteryl esters, a key step in the maturation of HDL and the process of reverse cholesterol transport (RCT) (Jonas, A., 2000, Biochemistry of Lipids, Lipoproteins and Membranes). In the context of cardiovascular disease, the depletion or dysfunction of HDL-associated PC can impair the body's ability to remove excess cholesterol from atherosclerotic plaques (Kontush & Chapman, 2006, Pharmacol Rev). Therapeutic interventions known as HDL mimetics or reconstituted HDL (rHDL), such as CSL112 and CER-001, utilize exogenous phosphatidylcholine complexed with apolipoprotein A-I to mimic the function of natural pre-beta HDL (Tardif et al., 2014, JAMA). These drugs aim to acutely increase cholesterol efflux capacity and reduce the burden of lipid-rich plaques in patients following acute coronary syndromes (Gibson et al., 2024, NEJM). By providing a surplus of PC, these therapies enhance the capacity of HDL to accept cholesterol from macrophages via the ABCA1 transporter and facilitate its subsequent esterification by LCAT (Rosenson et al., 2016, J Am Coll Cardiol). This mechanism is intended to stabilize vulnerable plaques and prevent recurrent ischemic events in high-risk cardiovascular patients.

Other names

Lecithin1,2-diacyl-sn-glycero-3-phosphocholineHDL-phospholipidsPhosphatidylcholine

Provision of essential phospholipid substrate for LCAT-mediated cholesterol esterification and facilitation of ABCA1-mediated cholesterol efflux from peripheral tissues as a component of reconstituted HDL particles.