Ezetimibe reduces cholesterol content and NF-kappaB activation in liver but not in intestinal tissue in guinea pigs

Journal of Inflammation

Research

Elisabeth Gröne¹  Hermann-Josef Gröne¹  Autar K. Walli²  Peter Fraunberger³  Heinz Drexel⁴ 

[1] Department of Cellular and Molecular Pathology, German Cancer Research Center, Heidelberg, Germany;Institute of Laboratory Medicine, Ludwig-Maximilians-University, Munich, Germany;Medical Central Laboratories, Carinagasse 41, A-6800, Feldkirch, Austria;Institute of Laboratory Medicine, Ludwig-Maximilians-University, Munich, Germany;Vorarlberger Institute of Vascular Investigation and Treatment (VIVIT), Dornbirn, Austria;

关键词: Inflammation;    Cholesterol;    Ezetimibe;    Guinea pigs;    Liver;    Intestine;   

DOI  :  10.1186/s12950-017-0150-y

 received in 2016-09-02, accepted in 2017-01-04,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundStatins (HMG CoA reductase inhibitors), in addition to reducing circulating cholesterol and incidence of coronary heart disease, also have pleiotropic, anti-inflammatory effects. Patients with chronic liver diseases, non-alcoholic fatty liver disease (NAFLD) or hepatitis C are often excluded from statin therapy because of adverse effects in a small cohort of patients despite increased cardiovascular risk cholesterol. Ezetimibe, which inhibits cholesterol absorption by inhibition of Niemann-Pick C1 like 1 (NPC1L1) protein in the brush border of intestinal cells, has been suggested as a new therapeutic option in these patients.MethodsEffects of ezetimibe on lipoprotein metabolism, hepatic and intestinal lipid content in guinea pigs, an animal model with a lipoprotein profile and pattern similar to humans were investigated. In order to investigate a possible effect of ezetimibe on cholesterol induced inflammation NF-kappaB activation as an indicator for inflammatory processes in liver and gut tissue was measured.ResultsLipid enriched diet led to accumulation of lipids in hepatic tissue which caused strong hepatic NF-kappaB activation. Ezetimibe reduced lipid diet induced increase of circulating cholesterol by about 77% and prevent hepatic NF-kappaB activation almost completely. In contrast in intestinal cells Ezetimibe, though lowering diet induced cholesterol accumulation, increased triglyceride content and subsequent NF-kappaB activation.ConclusionIn summary these data show, that ezetimibe effectively reduced diet induced circulating cholesterol levels, hepatic lipid accumulation and inflammatory response in our guinea pig model. However this drug elicited a local inflammatory response in intestinal tissue. Whether these diverse effects of ezetimibe on inflammatory parameters such as NF-kappaB have clinical relevance remains to be determined.

【 授权许可】

CC BY   
© The Author(s). 2017