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
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
Awarded by National Heart Foundation
Awarded by National Health and Medical Research Council of Australia
This work was supported by the National Heart Foundation (grant in aid G10S5192) and the National Health and Medical Research Council of Australia (program grant 1037903). P.C.N. Rensen is an Established Investigator of the Dutch Heart Foundation (2009T038).