Abstract
Although HDL is inversely correlated with coronary heart disease, elevated HDL-cholesterol is not always protective. Additionally, HDL has biological functions that transcend any antiatherogenic role: shotgun proteomics show that HDL particles contain 84 proteins (latest count), many correlating with antioxidant and anti-inflammatory properties of HDL. ApoA-I has been suggested to serve as a platform for the assembly of these protein components on HDL with specific functions - the HDL proteome. However, the stoichiometry of apoA-I in HDL subspecies is poorly understood. Here we use a combination of immunoaffinity chromatography data and volumetric analysis to evaluate the size and stoichiometry of LpA-I and LpA-I,A-II particles. We conclude that there are three major LpA-I subspecies: two major particles, HDL[4] in the HDL3 size range (d = 85.0 ± 1.2 Å) and HDL[7] in the HDL2 size range (d = 108.5 ± 3.8 Å) with apoA-I stoichiometries of 3 and 4, respectively, and a small minor particle, HDL[1] (d = 73.8 ± 2.1Å) with an apoA-I stoichiometry of 2. Additionally, we conclude that the molar ratio of apolipoprotein to surface lipid is significantly higher in circulating HDL subspecies than in reconstituted spherical HDL particles, presumably reflecting a lack of phospholipid transfer protein in reconstitution protocols.
Highlights
High density lipoproteins (HDL) is inversely correlated with coronary heart disease, elevated HDL-cholesterol is not always protective
Of LpA-I and LpA-I,A-II to the subspecies of HDL prepared by ultracentrifugation (17), we found that the two distinct subspecies of LpA-I corresponding to HDL[4] and HDL[7] in Fig. 1A, fall into the (HDL3a)gge and (HDL2b)gge size intervals, respectively
Gauthamadasa et al (7) results differ from ours in that they suggest that the entire population of LpA-I,A-II demonstrated the presence of only two proximal apoA-I molecules per particle, and we suggest two or three
Summary
HDL is inversely correlated with coronary heart disease, elevated HDL-cholesterol is not always protective. HDL has biological functions that transcend any antiatherogenic role: shotgun proteomics show that HDL particles contain 84 proteins (latest count), many correlating with antioxidant and anti-inflammatory properties of HDL. ApoA-I has been suggested to serve as a platform for the assembly of these protein components on HDL with specific functions - the HDL proteome. The stoichiometry of apoA-I in HDL subspecies is poorly understood. We use a combination of immunoaffinity chromatography data and volumetric analysis to evaluate the size and stoichiometry of LpA-I and LpA-I,A-II particles. We conclude that the molar ratio of apolipoprotein to surface lipid is significantly higher in circulating HDL subspecies than in reconstituted spherical HDL particles, presumably reflecting a lack of phospholipid transfer protein in reconstitution protocols.—Segrest, J. Volumetric determination of apolipoprotein stoichiometry of circulating HDL subspecies.
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