Structural and functional assessment of high-density lipoprotein heterogeneity

We studied the heterogeneity of high-density lipoproteins (HDL) in plasma of 110 subjects, using three different methods: (a) gradient gel electrophoresis (GGE); (b) electroimmunoassay, to measure the concentration of lipoprotein particles containing apoprotein (apo) AI but no apo-AII (LP AI); and (c) cholesterol esterification rate (FERHDL) in very-low- and low-density lipoprotein-depleted plasma. There were two study groups: patients with hypertension, whose plasma lipid profile was similar to their respective controls, and patients with hypoalphalipoproteinemia (hypoalpha), whose family members served as controls. Values for FERHDL were significantly higher in both risk groups than in their respective controls. LP AI was significantly decreased only in the hypoalpha subjects. Generally, LP AI and FERHDL were inversely related. LP AI correlated strongly with plasma HDL-cholesterol, apo AI, and LP AI/AII; FERHDL correlated with those values inversely. LP AI, but not FERHDL, correlated with HDL free cholesterol. On the other hand, FERHDL correlated strongly with plasma concentrations of triglycerides and with the plasma ratio of total/HDL-cholesterol while LP AI did not. GGE determination of the composition of HDL subspecies showed that both FERHDL and LP AI were significantly related to the content of HDL2b particles: FERHDL inversely, LP AI directly; the relative amount of HDL3b,c particles correlated only with FERHDL. We conclude that GGE and FERHDL can be used to quantify both the apparently protective (HDL2b) and risk-associated (HDL3b,c) particles, whereas the concentration of LP AI in plasma mainly reflects the concentration of the HDL2 subpopulation.