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

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 mice. Hyp..