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Muscle loss statin

Wei Wei, Adam G Schwaid, Xueqian Wang, Xunde Wang, Shili Chen, Qian Chu, Alan Saghatelian, Yihong Wan
Nuclear receptors (NRs) are key regulators of gene expression and physiology. Nearly half of all human NRs lack endogenous ligands including estrogen-related receptor α (ERRα). ERRα has important roles in cancer, metabolism, and skeletal homeostasis. Affinity chromatography of tissue lipidomes with the ERRα ligand-binding domain (LBD) and subsequent transcriptional assays identified cholesterol as an endogenous ERRα agonist. Perturbation of cholesterol biosynthesis or inhibition of ERRα revealed the interdependence of cholesterol and ERRα...
March 8, 2016: Cell Metabolism
Kristine M Erlandson, Ying Jiang, Sara M Debanne, Grace A McComsey
Heightened inflammation and immune activation are associated with lower bone mineral density (BMD) and lean body mass (LBM) among HIV-infected persons. We hypothesized that a reduction in inflammation with rosuvastatin would be associated with improvements in BMD and LBM. HIV-infected participants on stable antiretroviral therapy without statin indication and with heightened immune activation (≥19% CD8(+)CD38(+)HLA-DR(+) T cells) or inflammation (hsCRP ≥2 mg/liter) were randomized to rosuvastatin 10 mg daily or placebo for 96 weeks...
April 2016: AIDS Research and Human Retroviruses
Javier Rosada, Eleni Rebelos, Stefania Petruccelli, Marco Taddei
An 82-year-old white woman presented at our Internal Medicine ward with flaccid tetraparesis. Two months earlier, she had suffered a non-ST elevation myocardial infarction treated with percutaneous coronary intervention (PCI) and stenting, and she had been prescribed the classical post-PCI therapy (β-blockers, statins and antiplatelet agents). At admission, she was haemodynamically stable and the physical examination revealed reduced reflexes in the four limbs. Urgent laboratory findings revealed mild hypokalaemia...
2015: BMJ Case Reports
Mahmoud Salah Khalil, Nehal Khamis, Abdulmajeed Al-Drees, Hamza Mohammad Abdulghani
INTRODUCTION: In addition to their lipid-lowering effect, statins have pleiotropic effects that may extend their use to the treatment and prevention of various other diseases such as cancer, osteoporosis, multiple sclerosis, rheumatoid arthritis, type 2 diabetes, and Alzheimer's disease. Consequently, the number of patients taking statins is expected to increase. A side effect of statins, statin-induced myopathy, which may result from reduced muscular coenzyme Q10 levels, limits their use...
March 2015: Histology and Histopathology
Max E Davis, Michael A Korn, Jonathan P Gumucio, Julie A Harning, Anjali L Saripalli, Asheesh Bedi, Christopher L Mendias
BACKGROUND: Chronic rotator cuff tears are a common source of shoulder pain and disability, and patients with chronic cuff tears often have substantial weakness, fibrosis, inflammation, and fat accumulation. Identifying therapies to prevent the development of these pathologic processes will likely have a positive impact on clinical outcomes. Simvastatin is a drug with demonstrated anti-inflammatory and antifibrotic effects in many tissues but had not previously been studied in the context of rotator cuff tears...
February 2015: Journal of Shoulder and Elbow Surgery
Parmida Ranji, Manish Rauthan, Christophe Pitot, Marc Pilon
HMG-CoA reductase is the rate-limiting enzyme in the mevalonate pathway and the target of cholesterol-lowering statins. We characterized the C. elegans hmgr-1(tm4368) mutant, which lacks HMG-CoA reductase, and show that its phenotypes recapitulate that of statin treatment, though in a more severe form. Specifically, the hmgr-1(tm4368) mutant has defects in growth, reproduction and protein prenylation, is rescued by exogenous mevalonate, exhibits constitutive activation of the UPRer and requires less mevalonate to be healthy when the UPRmt is activated by a constitutively active form of ATFS-1...
2014: PloS One
Yves Allenbach, Laurent Drouot, Aude Rigolet, Jean Luc Charuel, Fabienne Jouen, Norma B Romero, Thierry Maisonobe, Odile Dubourg, Anthony Behin, Pascal Laforet, Tania Stojkovic, Bruno Eymard, Nathalie Costedoat-Chalumeau, Emmanuelle Campana-Salort, Anne Tournadre, Lucile Musset, Brigitte Bader-Meunier, Isabelle Kone-Paut, Jean Sibilia, Laurent Servais, Olivier Fain, Claire Larroche, Elisabeth Diot, Benjamin Terrier, Raphael De Paz, Antoine Dossier, Dominique Menard, Chafika Morati, Marielle Roux, Xavier Ferrer, Jeremie Martinet, Sophie Besnard, Remi Bellance, Patrice Cacoub, Laurent Arnaud, Bernard Grosbois, Serge Herson, Olivier Boyer, Olivier Benveniste
Necrotizing autoimmune myopathy (NAM) is a group of acquired myopathies characterized by prominent myofiber necrosis with little or no muscle inflammation. Recently, researchers identified autoantibodies (aAb) against 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) in patients with NAM, especially in statin-exposed patients. Here we report what is to our knowledge the first European cohort of patients with NAM.The serum of 206 patients with suspicion of NAM was tested for detection of anti-HMGCR aAb using an addressable laser bead immunoassay...
May 2014: Medicine (Baltimore)
Daniel H Katz, Sunny S Intwala, Neil J Stone
With the release of the 2013 American College of Cardiology/American Heart Association (ACC/AHA) Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults, emphasis has been placed on using evidence-based intensity of therapy to reduce atherosclerotic cardiovascular disease (ASCVD) risk, rather than focusing on goal cholesterol levels. Before initiating therapy, however, it is critical that physicians and patients discuss 4 key topics: (1) the benefit of ASCVD risk reduction, (2) medication adverse effects, (3) drug-drug interactions, and (4) patient preferences...
November 2014: Journal of Cardiovascular Pharmacology and Therapeutics
John D Clarke, Rhiannon N Hardwick, April D Lake, Andrew J Lickteig, Michael J Goedken, Curtis D Klaassen, Nathan J Cherrington
BACKGROUND & AIMS: A genome wide association study and multiple pharmacogenetic studies have implicated the hepatic uptake transporter organic anion transporting polypeptide-1B1 (OATP1B1) in the pharmacokinetics and musculoskeletal toxicity of statin drugs. Other OATP uptake transporters can participate in the transport of pravastatin, partially compensating for the loss of OATP1B1 in patients carrying the polymorphism. Non-alcoholic steatohepatitis (NASH) in humans and in a diet-induced rodent model alter the expression of multiple OATP transporters...
July 2014: Journal of Hepatology
Roberto Scarpioni, Marco Ricardi, Vittorio Albertazzi, Luigi Melfa
Several cardiovascular (CV) risk factors may explain the high rate of CV death among patients with chronic kidney disease (CKD). Among them both traditional and uremia-related risk factors are implicated and, moreover, the presence of kidney disease represents "per se" a multiplier of CV risk. Plasma lipid and lipoprotein profiles are changed in quantitative, but above all in qualitative, structural, and functional ways, and lipoprotein metabolism is influenced by the progressive loss of renal function. Statin therapy significantly reduces cholesterol synthesis and both CV morbidity and mortality either directly, by reducing the lipid profile, or via pleiotropic effects; it is supposed to be able to reduce both the progression of CKD and also proteinuria...
December 6, 2012: World Journal of Nephrology
Robert D Sanders, Amanda Nicholson, Sharon R Lewis, Andrew F Smith, Phil Alderson
BACKGROUND: Patients undergoing vascular surgery are a high-risk population with widespread atherosclerosis, an adverse cardiovascular risk profile and often multiple co-morbidities. Postoperative cardiovascular complications, including myocardial infarct (MI), are common. Statins are the medical treatment of choice to reduce high cholesterol levels. Evidence is accumulating that patients taking statins at the time of surgery are protected against a range of perioperative complications, but the specific benefits for patients undergoing noncardiac vascular surgery are not clear...
2013: Cochrane Database of Systematic Reviews
Alexander Dzien, Hannes Winner, Engelbert Theurl, Christine Dzien-Bischinger, Monika Lechleitner
OBJECTIVE: The aging-associated changes in body composition result in an increased cardiometabolic risk. A tremendous reduction of cardiovascular morbidity and mortality can be obtained by statin therapy. Statins are well tolerated, with myopathy as the most serious negative side effect. Some recently published studies indicate that the incidence of type 2 diabetes might be increased during intensified statin therapy. The aim of our study was to investigate whether statin therapy has an influence on the aging-associated changes in fat-free mass (FFM)...
2013: Obesity Facts
Elena Lesma, Silvia Ancona, Emanuela Orpianesi, Vera Grande, Anna Maria Di Giulio, Alfredo Gorio
Tuberous sclerosis complex (TSC) is a multi-systemic syndrome caused by mutations in TSC1 or TSC2 gene. In TSC2-null cells, Rheb, a member of the Ras family of GTPases, is constitutively activated. Statins inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase and block the synthesis of isoprenoid lipids with inhibition of Rheb farnesylation and RhoA geranylgeranylation. The effects of rosuvastatin on the function of human TSC2(-/-) and TSC2(-/meth) α-actin smooth muscle (ASM) cells have been investigated...
May 2013: Journal of Pharmacology and Experimental Therapeutics
Alister J McNeish, Francesc Jimenez-Altayo, Graeme S Cottrell, Christopher J Garland
BACKGROUND: In rat middle cerebral and mesenteric arteries the K(Ca)2.3 component of endothelium-dependent hyperpolarization (EDH) is lost following stimulation of thromboxane (TP) receptors, an effect that may contribute to the endothelial dysfunction associated with cardiovascular disease. In cerebral arteries, K(Ca)2.3 loss is associated with NO synthase inhibition, but is restored if TP receptors are blocked. The Rho/Rho kinase pathway is central for TP signalling and statins indirectly inhibit this pathway...
2012: PloS One
D Rosenbaum, J Dallongeville, P Sabouret, E Bruckert
BACKGROUNDS AND AIMS: To assess the burden of statin related muscular symptom in real life. METHODS AND RESULTS: We conducted a wide survey on 10,409 French subjects. Among these, 2850 (27%) had hypercholesterolemia and 1074 were treated with statins. Muscular symptoms were reported by 104 (10%) statin treated patients and led to discontinuation in 30% of the symptomatic patients. The main prescribed statins were low doses rosuvastatin, atorvastatin and simvastatin...
September 2013: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
Teresa Padró, Roberta Lugano, Maisa García-Arguinzonis, Lina Badimon
Growing human atherosclerotic plaques show a progressive loss of vascular smooth muscle cells (VSMC) becoming soft and vulnerable. Lipid loaded-VSMC show impaired vascular repair function and motility due to changes in cytoskeleton proteins involved in cell-migration. Clinical benefits of statins reducing coronary events have been related to repopulation of vulnerable plaques with VSMC. Here, we investigated whether HMG-CoA reductase inhibition with rosuvastatin can reverse the effects induced by atherogenic concentrations of LDL either in the native (nLDL) form or modified by aggregation (agLDL) on human VSMC motility...
2012: PloS One
M Francesca Notarangelo, N Marziliano, M Antonietta Demola, F Pigazzani, A Guidorossi, P Angelica Merlini, D Ardissino
WHAT IS KNOWN AND OBJECTIVE: The major clinical complication of statins is a variety of muscle complaints ranging from myalgia to rhabdomyolysis. There is growing evidence that carriers of genetic polymorphisms in the enzymes and transporters implicated in statin disposition, particularly the SLCO1B1 gene, are at increased risk of myotoxicity. Our objective is to report on two cases of statin-induced myopathy occurring in a family with two patients who are carriers of the loss of function SLCO1B1 genetic variant and to briefly review the related literature...
October 2012: Journal of Clinical Pharmacy and Therapeutics
Benjamin M Meador, Kimberly A Huey
INTRODUCTION: The most common side effect of statins, myopathy, is more likely in exercisers. We investigated the interaction of statin treatment with novel vs. accustomed exercise on muscle function, heat shock protein (Hsp) expression, and caspase activation. METHODS: Mice received daily cerivastatin or saline for 2 weeks, with/without wheel running (RW) (novel/sedentary). Accustomed groups completed 2 weeks of RW before statins. At 4 weeks, plantarflexor isometric force, Hsp25, αB-crystallin, caspase-3 and -9, and plasma creatine kinase (CK) were quantified...
December 2011: Muscle & Nerve
Hyo-Bum Kwak, Anna Thalacker-Mercer, Ethan J Anderson, Chien-Te Lin, Daniel A Kane, Nam-Sihk Lee, Ronald N Cortright, Marcas M Bamman, P Darrell Neufer
Statins, the widely prescribed cholesterol-lowering drugs for the treatment of cardiovascular disease, cause adverse skeletal muscle side effects ranging from fatigue to fatal rhabdomyolysis. The purpose of this study was to determine the effects of simvastatin on mitochondrial respiration, oxidative stress, and cell death in differentiated primary human skeletal muscle cells (i.e., myotubes). Simvastatin induced a dose-dependent decrease in viability of proliferating and differentiating primary human muscle precursor cells, and a similar dose-dependent effect was noted in differentiated myoblasts and myotubes...
January 1, 2012: Free Radical Biology & Medicine
Hisakuni Obayashi, Yoshikazu Nezu, Hatsue Yokota, Naoki Kiyosawa, Kazuhiko Mori, Naoyuki Maeda, Yoshiro Tani, Sunao Manabe, Atsushi Sanbuissho
3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are associated with adverse skeletal muscle toxicity, but the underlying mechanism remains unclear. To investigate the pathological mechanism of statin-induced myotoxicity, cerivastatin (20 ppm; corresponding to 2 mg/kg/day) was dietarily administered to young male F344 rats for 10 days, and time-course clinical observations, measurement of plasma creatine kinase activity, and light and electron microscopy of type I fiber-predominant skeletal muscle (soleus) or type II fiber-predominant skeletal muscles (extensor digitorum longus and tibialis anterior), were performed...
August 2011: Journal of Toxicological Sciences
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