Analysis of human plasma by gradient gel electrophoresis (GGE) revealed multiple distinct bands in the size range between very low density (VLDL) and low density lipoproteins (LDL). GGE of intermediate density lipoproteins (IDL) from normal subjects consistently showed two major bands with particle diameters in the range of 275 to 300 A. The larger, usually predominant subspecies was designated IDL-1, and the smaller, IDL-2. GGE also demonstrated two sizes of subpopulations in the VLDL density range in all subjects. A discontinuous nonequilibrium density gradient ultracentrifugation technique was devised to isolate a series of fractions containing progressively smaller lipoproteins. Successive fractions showed progressive enrichment in cholesteryl-esters, depletion of triglyceride, slower migration on agarose, and depletion of apo E and the C apolipoproteins relative to apo B. The IDL-1 and IDL-2 subspecies appeared to represent two distributions of lipoproteins overlapping in size (particle diameter 280-300 A and 268-284 A, respectively) and buoyant density (d = 1.008-1.022 g/ml and d = 1.013-1.028 g/ml, respectively). Plasma from two patients with dysbetalipoproteinemia showed predominant increases in fractions normally containing small VLDL and IDL-1, while patients with severe hypertriglyceridemia had increases primarily in levels of larger VLDL. Heterogeneity of lipoprotein precursors could account for the discrete subspecies of LDL observed in human plasma. (Arteriosclerosis

Serum concentrations of lipoprotein mass by flotation rate were measured in 12 long-distance runners and 64 sedentary men by analytic ultracentrifugation. The runners had significantly lower serum mass concentrations of the smaller, denser low-density lipoprotein particles of flotation rates S f 0-7 (including the LDL-II, LDL-III, and LDL-IV subspecies), very-low-density lipoprotein (VLDL) particles of S f 20-400, and high-density lipoprotein (HDL) particles of flotation rates F 1.20 0-1.5 (predominately the HDL3 subspecies), and higher serum mass concentrations of HDL particles with flotation rates between F 1.20 2.0-9.0 (including HDL 2a and HDL 2b and less dense particles belonging to HDL 3 ) than did sedentary men. Lipoprotein lipase activity was higher, and hepatic lipase activity was lower in runners than in the sedentary men. Thus, the effects of endurance exercise training to lower LDL may be specific to the smaller, denser LDL particle region. Similarities in the lipoprotein mass profiles of the runners and the low-risk profiles of sedentary, middle-aged women suggest the effects of common metabolic factors possibly leading to reduced risk of coronary artery disease.Long-distance running and other endurance activities are reported to elevate plasma concentrations of high-density lipoprotein (HDL) cholesterol, and to decrease plasma concentrations of low-density (LDL) and very-low-density lipoprotein (VLDL) cholesterol in men and women [1][2][3][4][5][6][7]. Previous studies of lipoproteins in relation to exercise have focused primarily on the measurements of the total cholesterol and various protein components of the HDL, LDL, and VLDL particles. These variables may not adequately portray the relationship of endurance exercise training to lipoprotein concentrations since there is much evidence to suggest that multiple subspecies of lipoprotein particles exist for these three lipoprotein species [8][9][10][11][12]. The technique of analytic ultracentrifugation may be used to estimate the serum mass concentrations of lipoprotein subspecies, and to measure directly the mass concentrations of finer subdivisions of very-low-density (14 intervals), intermediate-density (4 intervals), lowdensity (11 intervals), and high-density lipoproteins (15 intervals) by particle flotation rate. Differences in the serum lipoprotein mass concentrations of runners and sedentary men have not been previously reported for LDL and HDL subspecies, nor for individual flotation intervals within HDL, LDL, and VLDL particle regions. LIPOPROTEIN HETEROGENEITYThe traditional measurement LDL-cholesterol is a composite measurement that includes the cholesterol content of both the LDL (S f 0-12) and intermediate density lipoprotein (IDL, particles. Further heterogeneity within the LDL particle region (S f 0-l2) is evident from the presence of distinct isopycnic banding regions when LDL is subjected to density gradient ultracentrifugation, from the multiple bands that appear for gradient polyacrylamide gel electrophoresis of LDL, a...