Hypercholesterolemia pathophysiology

Lipoproteins
Lipoproteins are complex particles composed of a water-repelling core of mainly lipids as non-polar cholesterol esters (CEs) and triglycerides (TGs) surrounded by an amphipathic phospholipid monolayer that includes unesterified free cholesterol (FC) and proteins known as apolipoproteins or aproteins. Apolipoproteins provide a framework for lipoprotein assembly; determine the metabolic fate of the lipoprotein by activating or inhibiting key enzymes; and finally act as ligands for receptor molecules. Lipoproteins are classified into five classes, defined by their respective density on electrophoresis as Chylomicrons, Very Low Density Lipoproteins (VLDL), Intermediate Density Lipoproteins (IDL), Low Density Lipoprotein (LDL) and High Density Lipoproteins (HDL).

Apolipoproteins
Apolipoproteins are classified by an alphabetical designation (A through E) with a Roman numeral suffix defined by the order in which the apolipoprotein emerges from a chromatographic column:


 * ApoA-I: principal structural protein of HDL but also found in chylomicrons and activates lecithin:cholesterol acyltransferase (LCAT).
 * ApoA-II: another structural protein of HDL also found in chylomicrons and activates hepatic lipase (HL).
 * ApoA-IV: predominantly found in HDL and activates LCAT and lipoprotein lipase (LPL).
 * ApoB-48: exclusively found in chylomicrons, derived from the apoB-100 gene, and reduced to 48% of the N-terminal component of B-100 by RNA editing, with no LDL receptor (LDLr) binding domain.
 * ApoB-100: principal structural protein of LDL, alsofound in VLDL, IDL, and Lp(a); ligand for LDLr.
 * ApoC-I: primarily found in HDL and chylomicrons and also in IDL and VLDL and activates LCAT.
 * ApoC-II: protein primarily of VLDL and chylomicrons and also found in HDL and IDL and activates LPL.
 * ApoC-III: found broadly in HDL, IDL, LDL, VLDL, and chylomicrons but more consistently in VLDL and chylomicrons and inhibits LPL.
 * ApoD: exclusively found in HDL and possibly activates CE transfer protein (CETP).
 * ApoE: also found broadly in HDL, IDL, LDL, VLDL, and chylomicrons and binds to LDLr with varying affinity dependent on the inherited apoE allele. Three different apoE isoforms exist in humans: apoE2 with lower affinity to LDLr, apoE3 with intermediate binding affinity, and apoE4 with higher affinity.
 * Apo(a): distinguishing structural protein of Lp(a) that is covalently bound to apoB-100 and inhibits plasminogen activation

Apolipoprotein Classification: