Examination of LDL receptor Activity by Mitogen-Stimulated Proliferation of Lymphocytes in the Presence of HMG-CoA Reductase Inhibitor, Compactin
Makoto C. Nagano, Hiroaki Hattori, Tohru Egashira, Hideaki Kurata, Kazuo N. Kondo, Hiroshige Itakura · The Journal of Japan Atherosclerosis Society · 1995
Lipsky et al. developed a simplified method to detect LDL receptor defects by the measurement of lymphocyte proliferation depending on exogenous LDL cholesterol using mevinolin to suppresse sterol biosynthesis. We examined using Compactin, a HMG-CoA reductase inhibitor, instead of mevinolin, whether their method could be used for the detection of LDL receptor defects in peripheral lymphocytes of familial hypercholesterolemia (FH) or not. The mitogen stimulated proliferation of lymphocytes from a patient with homozygous FH was significantly impaired in comparison with those in normolipidemias. The difference in proliferation pattern depending on LDL cholesterol in lymphocytes between patients with heterozygous FH and normolipidemias was significant and the phenotype of heterozygous and homozygous FH could be identified.The percent of recovery on lymphocyte proliferation at the concentration of 3μg/ml LDL cholesterol, as the LDL receptor activity, was compared with the receptor activity on DiI-LDL uptake in lymphocytes by flow cytometry. There was a good correlation (γ=0.783) between the two methods.These findings suggest that the method of lymphocyte proliferation using compactin is less complicated than the conventional radioreceptor assay and can be useful clinically for the measurement of LDL receptor function in FH. In addition, this method has approximately the same sensitivity and specificity as the method on DiI-LDL uptake by flow cytometry.