title: Surface expression of low density lipoprotein receptor in EBV-transformed lymphocytes: characterization and use for studying familial hypercholesterolemia.
abstract: The objectives of the present study were to characterize the surface expression of low density lipoprotein receptor (LDL-R) in Epstein-Barr virus transformed lymphocytes (EBV-L) and to determine the applicability of the cellular system for the study of familial hypercholesterolemia. The EBV-L subsets and LDL-R expression were determined by immuno-cytofluorimetry. The LDL-R expression in EBV-L which consisted of mostly B cells was no different among antigenic subsets. EBV-L cultured in lipoprotein deficient serum demonstrated a 9.3-fold higher LDL-R expression than primary lymphocytes. Lovastatin caused an additional 1.9-and 1.4-fold increase in EBV-L and primary lymphocytes respectively. This difference in lovastatin response is statistically significant (paired t-test, P < 0.001). 54% of the high LDL-R expression in EBV-L was related to the changes in proliferation measured as stimulation index (SI). LDL and lovastatin modulated the LDL-R expression without affecting 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.
authors.affiliation: Department of Pediatrics and Medical Genetics, University of Calgary, Alberta, Canada.
authors.forename: P
authors.initials: P
authors.lastname: Chan
authors.forename: C
authors.initials: C
authors.lastname: Jones
authors.forename: R
authors.initials: R
authors.lastname: Lafrenière
authors.forename: H G
authors.initials: HG
authors.lastname: Parsons
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism* / Q000821:virology; D018929:Cell Culture Techniques; D002455:Cell Division; D002462:Cell Membrane / Q000378:metabolism; D002472:Cell Transformation, Viral; D002648:Child; D004247:DNA / Q000032:analysis; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D004854:Herpesvirus 4, Human / Q000502:physiology; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D008148:Lovastatin / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D011973:Receptors, LDL / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D000924:Anticholesteremic Agents; D011973:Receptors, LDL; D004247:DNA; D008148:Lovastatin