SURFACE EXPRESSION OF LOW-DENSITY-LIPOPROTEIN RECEPTOR IN EBV-TRANSFORMED LYMPHOCYTES - CHARACTERIZATION AND USE FOR STUDYING FAMILIAL HYPERCHOLESTEROLEMIA

The objectives of the present study were to characterize the surface e xpression of low density lipoprotein receptor (LDL-R) in Epstein-Barr virus transformed lymphocytes (EBV-L) and to determine the applicabili ty of the cellular system for the study of familial hypercholesterolem ia. The EBV-L subsets and LDL-R expression were determined by immuno-c ytofluorimetry. The LDL-R expression in EBV-L which consisted of mostl y B cells was no different among antigenic subsets. EBV-L cultured in lipoprotein deficient serum demonstrated a 9.3-fold higher LDL-R expre ssion than primary lymphocytes. Lovastatin caused an additional 1.9-an d 1.4-fold increase in EBV-L and primary lymphocytes respectively. Thi s difference in lovastatin response is statistically significant (pair ed t-test, P < 0.001). 54% Of the high LDL-R expression in EBV-L was r elated to the changes in proliferation measured as stimulation index ( SI). LDL and lovastatin modulated the LDL-R expression without affecti ng SI. FH subjects demonstrated 2% (homozygote, n = 1) and 44.6 +/- 12 .3% (heterozygotes, n = 35) in LDL-R expression of controls (n = 30). This maintenance of the FH phenotype and the intrinsically high LDL-R expression in EBV-L make the cellular system suitable for the study of FH as well as the regulation of LDL-R. (C) 1997 Elsevier Science Irel and Ltd.