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Statins and liver

Estela Lorza-Gil, Jane C de Souza, Marta García-Arévalo, Jean F Vettorazzi, Ana Carolina Marques, Alessandro G Salerno, Jose Roberto Trigo, Helena C F Oliveira
New onset of diabetes is associated with the use of statins. We have recently demonstrated that pravastatin-treated hypercholesterolemic LDL receptor knockout (LDLr-/- ) mice exhibit reductions in insulin secretion and increased islet cell death and oxidative stress. Here, we hypothesized that these diabetogenic effects of pravastatin could be counteracted by treatment with the antioxidant coenzyme Q 10 (CoQ 10 ), an intermediate generated in the cholesterol synthesis pathway. LDLr -/- mice were treated with pravastatin and/or CoQ 10 for 2 months...
December 7, 2018: Journal of Cellular Physiology
Mary E Rinella, James F Trotter, Manal F Abdelmalek, Angelo H Paredes, Margery A Connelly, Mark J Jaros, Lei Ling, Stephen J Rossi, Alex M DePaoli, Stephen A Harrison
BACKGROUND: NGM282, an engineered analogue of the gut hormone FGF19, improves hepatic steatosis and fibrosis biomarkers in patients with nonalcoholic steatohepatitis (NASH). However, NGM282 increases serum cholesterol levels by inhibiting CYP7A1, which encodes the rate-limiting enzyme in the conversion of cholesterol to bile acids. Here, we investigate whether administration of a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor can manage the cholesterol increase seen in NASH patients treated with NGM282...
December 7, 2018: Journal of Hepatology
Erika Gurzeler, Einari Aavik, Anssi Laine, Teemu Valkama, Henri Niskanen, Jenni Huusko, Minna U Kaikkonen, Seppo Ylä-Herttuala
Statins are effective drugs used to prevent and treat cardiovascular diseases but their effects in the absence of low density lipoprotein receptor (LDLR) and on the risk of diabetes are not yet well characterized. The aim of this study was to clarify systemic and pleiotropic effects of rosuvastatin on cardiovascular and diabetic phenotypes. IGF-II/LDLR-/- ApoB100/100 hypercholesterolemic prediabetic mice were used to test the effects of rosuvastatin on plasma glucose, insulin, lipids, atherosclerosis and liver steatosis...
November 30, 2018: Biochimica et biophysica acta. General subjects
Knut Stokkeland, Jonas Höijer, Matteo Bottai, Karin Söderberg-Löfdal, Annika Bergquist
BACKGROUND & AIMS: There is increasing evidence that statins can benefit patients with chronic liver diseases, but their effects have not been studied in patients with primary sclerosing cholangitis (PSC). We performed a nationwide study in Sweden to determine the effects of exposure to drugs, including statins, in patients with PSC. METHODS: We studied a population-based cohort of patients in Sweden with PSC and concomitant ulcerative colitis or Crohn´s disease from 2005 through 2014 (n=2914), followed through 2016...
November 15, 2018: Clinical Gastroenterology and Hepatology
Liping Qu, Didi Li, Xiaoping Gao, Yongwei Li, Jianming Wu, Wenjun Zou
Numerous risk factors are responsible for the development of atherosclerosis, for which an increased serum level of low-density lipoprotein cholesterol (LDL-C) is a driving force. By binding to the low-density lipoprotein cholesterol receptor (LDLR) and inducing LDLR degradation, proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a key role in cholesterol homeostasis regulation. The inducement of PCSK9 expression is also an important reason for statin intolerance. The Di'ao Xinxuekang (DXXK) capsule extracted from Dioscorea nipponica Makino is a well-known traditional Chinese herbal medicinal product used in atherosclerotic cardiovascular disease...
2018: Frontiers in Pharmacology
Colin H Beckwitt, Amanda M Clark, Bo Ma, Diana Whaley, Zoltán N Oltvai, Alan Wells
BACKGROUND: Metastasis in breast cancer foreshadows mortality, as clinically evident disease is aggressive and generally chemoresistant. Disseminated breast cancer cells often enter a period of dormancy for years to decades before they emerge as detectable cancers. Harboring of these dormant cells is not individually predictable, and available information suggests that these micrometastatic foci cannot be effectively targeted by existing therapies. As such, long-term, relatively non-toxic interventions that prevent metastatic outgrowth would be an advance in treatment...
October 2018: British Journal of Cancer
Bhavin B Adhyaru, Terry A Jacobson
The 2013 ACC/AHA guidelines on blood cholesterol management were a major shift in the delineation of the main patient groups that could benefit from statin therapy and emphasized the use of higher-intensity statin therapies. In 2016, an expert consensus panel from the ACC recommended the use of nonstatin therapies (ezetimibe and PCSK9 inhibitors) in addition to maximally tolerated statin therapy in individuals whose LDL-cholesterol and non-HDL-cholesterol levels remained above certain thresholds after statin treatment...
December 2018: Nature Reviews. Cardiology
Danxin Wang, Katherine Hartmann, Michal Seweryn, Wolfgang Sadee
BACKGROUND: CYP7A1 (cholesterol 7α-hydroxylase) catalyzes the rate-limiting step in bile acid biosynthesis from cholesterol-a main pathway for cholesterol removal from the body. CYP7A1 single-nucleotide polymorphisms (SNPs) are associated with total cholesterol and LDL (low-density lipoprotein) levels, risk of cardiovascular diseases, and other phenotypes; however, results are inconsistent, and causative variants remain uncertain, except for a frequent promoter SNP (rs3808607). METHODS: We used chromatin conformation capture (4C assay), chromatin immunoprecipitation qPCR assay in hepatocytes, and CRISPR (clustered regularly interspaced short palindromic repeats)-mediated genome editing in hepatocellular carcinoma cell line cells to identify regulatory regions for CYP7A1...
October 2018: Circulation. Genomic and precision medicine
Jian Liu, Haoyue Huang, Sheng Shi, Xu Wang, Yunsheng Yu, Yanqiu Hu, Jiacheng Sun, Chuanlu Ren, Junjie Yang, Zhenya Shen
Apolipoprotein M (apoM) is a recently identified human apolipoprotein that is associated with the formation of high-density lipoprotein (HDL). Studies have demonstrated that statins may affect the expression of apoM; however, the regulatory effects of statins on apoM are controversial. Furthermore, the underlying mechanisms by which statins regulate apoM remain unclear. In the present study, in vivo and in vitro models were used to investigate whether the anti-atherosclerotic effects of statins are associated with its apoM-regulating effects and the underlying mechanism...
November 2018: Experimental and Therapeutic Medicine
Ki Hoon Han
HMG-CoA reductase inhibitors, i.e. statins, are effective in reducing cardiovascular disease events but also in cardiac-related and overall mortality. Statins are in general well-tolerated, but currently the concerns are raised if statins may increase the risk of new-onset diabetes mellitus (NOD). In this review, the possible effects of statins on organs/tissues being involved in glucose metabolism, i.e. liver, pancreas, adipose tissue, and muscles, had been discussed. The net outcome seems to be inconsistent and often contradictory, which may be largely affected by in vitro experimental settings or/and in vivo animal conditions...
November 2018: Korean Circulation Journal
Aimei Liu, Qinghua Wu, Jingchao Guo, Irma Ares, José-Luis Rodríguez, María-Rosa Martínez-Larrañaga, Zonghui Yuan, Arturo Anadón, Xu Wang, María-Aránzazu Martínez
Statins, 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, are currently the most effective lipid-lowering drugs, effectively reducing the plasma total cholesterol and low-density lipoprotein, while also decreasing three triacylglycerols and increasing plasma high-density lipoprotein to a certain extent. However, the excessive or long-term use of statins can cause in vitro cytotoxicity, in vivo liver injury, liver necrosis, kidney damage, and myopathy in both human beings and animals. Many studies indicate that oxidative stress is involved in the various toxicities associated with statins, and various antioxidants have been evaluated to investigate their protective roles against statin-induced liver, kidney, and muscle toxicities...
October 12, 2018: Pharmacology & Therapeutics
Eleni Theocharidou, Marianna Papademetriou, Andromachi Reklou, Alexandros Sachinidis, Chrisoula Boutari, Olga Giouleme
BACKGROUND: Statin treatment exhibits a beneficial effect on non-alcoholic fatty liver disease (NAFLD) and on cardiovascular disease (CVD) in patients with NAFLD. OBJECTIVE: The aim of this review is to summarize the role of proprotein convertase subtilisin kexin type-9(PCSK9) in the pathogenesis of NAFLD and discuss the effects of the new hypolipidaemic drugs PCSK9 inhibitors on NAFLD. RESULTS: Data indicates that high intrahepatic or circulating PCSK9 levels increase muscle and liver lipid storage, adipose energy storage and hepatic fatty acids, as well as triglycerides storage and secretion, thus contributing to the pathogenesis of NAFLD...
October 10, 2018: Current Pharmaceutical Design
Thomas Gossios, Ioanna Zografou, Veta Simoulidou, Athina Pirpassopoulou, Konstantinos Christou, Asterios Karagiannis
BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal-dominant genetic disease, associated with premature atherosclerotic cardiovascular disease (CVD), especially in its homozygous type (HoFH). OBJECTIVE: The aim of this review is to discuss the safety and efficacy of combination treatments (procedures and drugs) for HoFH. RESULTS: Historically, liver transplantation was used first; however, it is currently considered only as a last resort for some patients...
October 8, 2018: Current Pharmaceutical Design
Christian Labenz, Yvonne Huber, Eva Kalliga, Michael Nagel, Christian Ruckes, Beate K Straub, Peter R Galle, Marcus-Alexander Wörns, Quentin M Anstee, Detlef Schuppan, Jörn M Schattenberg
BACKGROUND: Advanced fibrosis has been established as the most important predictor of overall mortality in patients with non-alcoholic fatty liver disease (NAFLD). In contrast to cirrhosis, advanced, non-cirrhotic NAFLD is difficult to identify and data from Germany are lacking. AIM: To identify clinical factors associated with advanced, non-cirrhotic fibrosis. METHODS: Patients were recruited in the prospectively enrolling European NAFLD Registry...
November 2018: Alimentary Pharmacology & Therapeutics
Omer Shahab, Rakesh Biswas, James Paik, Haley Bush, Pegah Golabi, Zobair M Younossi
Dyslipidemia is one of the common risk factors for NAFLD and is associated with cardiovascular (CV) mortality, which is the most common cause of death in NAFLD. Lipid-lowering agents (LLAs) are used to reduce CV events in the general population. Our aim was to assess whether the use of LLAs in patients with NAFLD can reduce the risk of CV mortality. We used the third National Health and Nutrition Examination Survey mortality linked files. Mortality was determined from the National Death Index records through 2011...
October 2018: Hepatology communications
Kosuke Sawami, Atsushi Tanaka, Tsukasa Nakamura, Eiichi Sato, Yoshihiko Ueda, Koichi Node
Dyslipidemia is often complicated by chronic kidney disease (CKD). Lipid-lowering medications may be effective, in part, for inhibiting development and progression of CKD. Ezetimibe, a cholesterol absorption inhibitor, has pleiotropic actions, including anti-inflammatory and anti-oxidant effects, contributing to a decreased risk of cardiovascular diseases. A 40-year-old woman was admitted with dyslipidemia and macroproteinuria, whose samples of renal biopsy showed exudative lesions, but without glomerular basement membrane thickening or nodular lesions, in some glomeruli...
June 2018: Journal of Cardiology Cases
Jiayin Yang, Lai-Yung Wong, Xiao-Yu Tian, Rui Wei, Wing-Hon Lai, Ka-Wing Au, Zhiwei Luo, Carl Ward, Wai-In Ho, David P Ibañez, Hao Liu, Xichen Bao, Baoming Qin, Yu Huang, Miguel A Esteban, Hung-Fat Tse
Familial hypercholesterolemia (FH) is mostly caused by low-density lipoprotein receptor (LDLR) mutations and results in an increased risk of early-onset cardiovascular disease due to marked elevation of LDL cholesterol (LDL-C) in blood. Statins are the first line of lipid-lowering drugs for treating FH and other types of hypercholesterolemia, but new approaches are emerging, in particular PCSK9 antibodies, which are now being tested in clinical trials. To explore novel therapeutic approaches for FH, either new drugs or new formulations, we need appropriate in vivo models...
September 15, 2018: Journal of Visualized Experiments: JoVE
Martina Cebova, Radoslava Rehakova, Michaela Kosutova, Olga Pechanova
Current treatments for cardiovascular and obesity-associated diseases, such as statin therapy, may be associated with several side effects. Products from food sources with polyphenolic compounds may represent promising agents in the treatment of cardiovascular and metabolic diseases with minimal side effects. Thus, we aimed to study the effect of sesame oil and simvastatin treatment on plasma lipid profile, nitric oxide generation, and oxidative load in obese Zucker rats. 12-week-old male Zucker rats were divided into the control and sesame oil- (1...
2018: Oxidative Medicine and Cellular Longevity
Laurie R Braun, Meghan N Feldpausch, Natalia Czerwonka, Julian Weiss, Karen Branch, Hang Lee, Edgar L Martinez-Salazar, Martin Torriani, Craig A Sponseller, Steven K Grinspoon, Takara L Stanley
Context: 3-Hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors (statins) are widely prescribed. Statins may have important metabolic effects on insulin sensitivity and liver fat, but limited studies have assessed these effects by using euglycemic hyperinsulinemic clamp, stable isotopes, and 1H magnetic resonance spectroscopy (MRS) for liver fat quantification. Objective: To study the effects of pitavastatin on hepatic fat and insulin sensitivity. Design: Six-month, double-blind, randomized, placebo-controlled trial...
November 1, 2018: Journal of Clinical Endocrinology and Metabolism
Niki Katsiki, Dimitri P Mikhailidis
The past decade has witnessed considerable progress in the field of lipids. New drugs have been "rapidly" developed and some of these drugs have already been evaluated in event-based large trials. This evidence has led to the guidelines recommending new, more aggressive treatment goals for low-density lipoprotein cholesterol (LDL-C) levels. Although LDL-C remains the principal goal for cardiovascular disease (CVD) risk reduction, there has also been considerable interest in other lipid variables, such as high-density lipoprotein cholesterol, triglycerides, and lipoprotein(a)...
September 18, 2018: Hormones: International Journal of Endocrinology and Metabolism
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