Journal article

Low-Density Lipoprotein Receptor-Dependent and Low-Density Lipoprotein Receptor-Independent Mechanisms of Cyclosporin A-Induced Dyslipidemia

Maaike Kockx, Elias Glaros, Betty Leung, Theodore W Ng, Jimmy FP Berbee, Virginie Deswaerte, Diana Nawara, Carmel Quinn, Kerry-Anne Rye, Wendy Jessup, Patrick CN Rensen, Peter J Meikle, Leonard Kritharides

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY | LIPPINCOTT WILLIAMS & WILKINS | Published : 2016

Abstract

OBJECTIVE: Cyclosporin A (CsA) is an immunosuppressant commonly used to prevent organ rejection but is associated with hyperlipidemia and an increased risk of cardiovascular disease. Although studies suggest that CsA-induced hyperlipidemia is mediated by inhibition of low-density lipoprotein receptor (LDLr)-mediated lipoprotein clearance, the data supporting this are inconclusive. We therefore sought to investigate the role of the LDLr in CsA-induced hyperlipidemia by using Ldlr-knockout mice (Ldlr(-/-)). APPROACH AND RESULTS: Ldlr(-/-) and wild-type (wt) C57Bl/6 mice were treated with 20 mg/kg per d CsA for 4 weeks. On a chow diet, CsA caused marked dyslipidemia in Ldlr(-/-) but not in wt m..

View full abstract