Influence of cyclosporine on low-density lipoprotein uptake in human lymphocytes

Abstract

Low-density lipoprotein (LDL) levels are often elevated in renal transplant recipients, and cyclosporine (CsA) therapy in these patients has been implicated. Cardiovascular disease is the major cause of mortality in transplant recipients, and alterations of lipid metabolism represent a common risk factor. The role of CsA on LDL metabolism is still partially defined. The aim of the study was to evaluate the LDL receptor uptake of CsA-transported LDL (CsA-LDL) compared with normal LDL in normal and CsA-treated lymphocytes. Forty-seven healthy unrelated subjects and 6 CsA-treated patients were consecutively enrolled as donors of lymphocytes to measure receptor-mediated LDL metabolism. Normal LDL and CsA-LDL were isolated from blood donors and from patients under CsA immunosuppressive therapy, respectively. Lipoproteins were labeled with a fluorochrome, and LDL receptor uptake was measured by flow cytometry. Normal LDL uptake was 13.95% ± 4.5%, whereas CsA-LDL uptake was 32.47% ± 10.84% ( P < .001) in healthy lymphocytes. In CsA-treated lymphocytes, normal LDL uptake was 7.48% ± 2.32% vs 12.49% ± 2.44% CsA-LDL ( P < .01). Lymphocytes of every subject showed at least a 2-fold increased uptake of CsA-LDL vs normal LDL. Our data show that CsA-LDL is internalized more than normal LDL via the LDL receptor in both human healthy and CsA-treated lymphocytes. CsA-treated lymphocytes, in comparison to normal lymphocytes, exhibit a reduced LDL receptor activity.