REMNANT-LIKE VERY-LOW-DENSITY LIPOPROTEIN ISOLATED FROM HYPERTRIGLYCERIDEMIC PATIENTS BY IMMUNOAFFINITY CHROMATOGRAPHY SUPPRESSED 3-HYDROXY-3-METHYLGLUTARYL COENZYME-A ACTIVITY OF CULTURED HUMAN SKIN FIBROBLASTS

It has been previously reported that VLDL unbound to monoclonal antibo dy against apoB-100 was rich in apoE, thus resembling remnant particle s (J Lipid Res, 1993:33;369-380). In the current study, we have furthe r analyzed the unbound VLDL fraction in plasma from hypertriglyceridem ic patients using a mixture of monoclonal antibodies against apoB-100 and apoA-1. The unbound VLDL isolated from the plasma of hypertriglyce ridemic patients was found to be rich in apoE, apoB-48, and triglyceri de compared with the bound VLDL. Furthermore, these unbound VLDL, but not bound VLDL, significantly suppressed HMG CoA reductase activity of cultured human skin fibroblasts (-20 to -25%, P = 0.0022). The degree of suppression is significantly correlated with the apoE content of u nbound VLDL (r = -0.769, P < 0.05). Unbound VLDL failed to suppress th e activity of HMG CoA reductase of LDL receptor negative fibroblasts. These observations indicate a potential atherogenicity of remnant-like unbound VLDL by delivering more cholesterol through the LDL receptor dependent pathway with apoE as a ligand. In conclusion, this new immun oaffinity chromatography system is a useful method for directly quanti fying atherogenic remnants in plasma. (C) 1997 Elsevier Science B.V.