Exploiting the Vascular Protective Effects of High-Density Lipoprotein and its Apolipoproteins

Abstract

HDL cholesterol particles consist of an outer amphipathic layer of free cholesterol, phospholipid, and several apolipoproteins (apolipoprotein A-I [the most abundant] and apolipoproteins AII, C, E, AIV, J [clusterin], and D) on the surface, with a triglyceride and cholesterol ester–rich hydrophobic core. Apolipoprotein A-I constitutes ≈70% and apolipoprotein A-II makes up ≈20% of the protein content of HDL. Apolipoprotein A-I is synthesized in the liver and intestines in man and mice (and mostly in the intestines in rabbits), whereas apolipoprotein A-II is synthesized mostly in the liver. The gene for apolipoprotein A-I is located on chromosome 11 adjacent to the gene cluster for apolipoproteins CIII and A-IV. Apolipoprotein A-I is synthesized as a 260-amino acid prepropeptide, which is cleaved to a 249-amino acid propeptide, which in turn is cleaved to the 243-amino acid, mature apolipoprotein A-I after secretion out of the cell.