Muscle loss statin

Traditional serum biomarkers used to assess skeletal muscle damage, such as activity of creatine kinase (CK), lack tissue specificity and sensitivity, hindering early detection of drug-induced myopathies. Recently, a novel four-factor skeletal muscle injury panel (MIP) of biomarkers consisting of skeletal troponin I (sTnI), CK mass (CKm), fatty acid binding protein 3 (Fabp3), and myosin light chain 3 (Myl3), has been shown to have increased tissue specificity and sensitivity in rodent models of skeletal muscle injury...

Statins are among the most commonly prescribed drugs for the treatment of high blood cholesterol. Myotoxicity of statins in certain individuals is often a severe side effect leading to withdrawal. Using C2C12 and H9c2 cells, both exhibiting characteristics of skeletal muscle cells, we addressed whether resveratrol (RSV) can prevent statin toxicity. Statins decreased cell viability in a dose and time-dependent manner. Among the five statins tested, atorvastatin, simvastatin, lovastatin, pravastatin, and fluvastatin, simvastatin is the most toxic one...

BACKGROUND: Palbociclib is a selective well-tolerated antineoplastic drug used in the treatment of advanced HER2-negative, estrogen-receptor positive breast cancer that has shown significant improvement in progression-free survival. We present a patient that developed severe rhabdomyolysis with tetra-affection and loss of gait after initiating the first cycle of Palbociclib concomitantly with Simvastatin 40 mg treatment. CASE PRESENTATION: A 71-year-old woman with metastatic breast cancer developed tetraparesis and near fatal rhabdomyolysis after initiation of first cycle Palbociclib...

CONTEXT: Heart failure (HF) is rapidly increasing in incidence and is often present in patients receiving long-term statin therapy. OBJECTIVE: To test whether or not patients with HF on long-term statin therapy respond to discontinuation of statin therapy and initiation of coenzyme Q10 (CoQ10 ) supplementation. DESIGN: We prospectively identified patients receiving long-term statin therapy in whom HF developed in the absence of any identifiable cause...

The deleterious effects of statins on skeletal muscle are well known, but the mechanism associated with these effects remains unresolved. Statins are associated with mitochondrial damage, which may contribute to muscle myopathy. Here we demonstrate that simvastatin induces mitophagy in skeletal muscle cells and hypothesized that attenuating this process by silencing the mitophagy adapter p62/sequestosome-1 (SQSTM1) might mitigate myotoxicity. Surprisingly, silencing p62/SQSTM1 in differentiated C2C12 muscle cells exacerbated rather than attenuated myotoxicity...

Statin-associated necrotizing autoimmune myositis (NAM) is an autoimmune condition characterized by severe acute-onset proximal muscle weakness, a very high creatinine kinase (CK) level, and prominent myofiber necrosis and minimal lymphocytic infiltration on muscle biopsy. Unlike self-limited statin myopathy, this condition usually requires aggressive immunomodulation therapy to assist recovery and prevent future disability. In this case report, we present a patient who developed progressive muscle weakness after taking atorvastatin for one year...

The present study is centered on molecular mechanisms of the cytoprotective effect of geranylgeraniol (GGOH) in skeletal muscle harmed by statin-associated myopathy (SAM). GGOH via autophagy induction was purportedly assumed to prevent skeletal muscle viability impaired by statins, atorvastatin (ATR) or simvastatin (SIM). The C2C12 cell line was used as the 'in vitro' model of muscle cells at different stages of muscle formation, and the effect of ATR or SIM on the cell viability, protein expression and mitochondrial respiration were tested...

The mechanisms that underlie the pathophysiology of aging, amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD) and stroke are not fully understood and have been the focus of intense and constant investigation worldwide. Studies that provide insights on aging and age-related disease mechanisms are critical for advancing novel therapies that promote successful aging and prevent or cure multiple age-related diseases. The April 2019 issue of the journal, "Aging & Disease" published a series of articles that confer fresh insights on numerous age-related conditions and diseases...

The repair capacity of progenitor skeletal muscle satellite cells (SC) in Type 1 diabetes mellitus (T1DM) is decreased. This is associated with the loss of skeletal muscle function. In T1DM, the deficiency of C-peptide along with insulin is associated with an impairment of skeletal muscle functions such as growth, and repair, and is thought to be an important contributor to increased morbidity and mortality. Recently, cholesterol-lowering drugs (statins) have also been reported to increase the risk of skeletal muscle dysfunction...

The present study investigated the cytotoxic effects of statins (atorvastatin (ATR) and simvastatin (SIM), resp.) and methyl-beta-cyclodextrin (M β CD), at their respective IC50 concentrations, on muscle regeneration in the in vitro model of murine C2C12 myoblasts. Cotreatment with mevalonate (MEV), farnesol (FOH), geranylgeraniol (GGOH), or water-soluble cholesterol (Chol-PEG) was employed to determine whether the statin-dependent myotoxicity resulted from the lower cholesterol levels or the attenuated synthesis of intermediates of mevalonate pathway...

The inflammatory myopathies, which include dermatomyositis, polymyositis, and the immune-mediated necrotizing myopathies, are a heterogeneous group of autoimmune diseases that manifest with muscle, skin, or lung damage. Collectively, these autoimmune diseases result from loss of tolerance to a select group of self-antigens, although the precise mechanism through which this occurs is not known. Infection, malignancy, and certain medications including statins and the immune checkpoint inhibitors used in cancer therapy have been identified as potential immunologic triggers of the inflammatory myopathies...

Statins, inhibitors of hydroxy methyl glutaryl coenzyme-A (HMG-CoA) reductase, are the most widely used drugs for treating hypercholesterolemia. However, statins can cause disabling myopathy as their main adverse effect. Several molecular mechanisms underlie the statin-induced myopathy including the decrease in the levels of essential mevalonate and cholesterol derivatives. This review discusses a further mechanism involving the loss of other anti-oxidant defenses besides ubiquinone (Co-Q) in skeletal muscles which produce a significant amount of reactive oxygen species (ROS)...

Airway remodeling in asthma contributes to airway hyperreactivity, loss of lung function and persistent symptoms. Current therapies do not adequately treat the structural airway changes associated with asthma. Statin drugs have improved respiratory health and their therapeutic potential in asthma has been tested in clinical trials. However, the mechanism of action of statins in this context has remained elusive. The present study hypothesized that atorvastatin treatment of ovalbumin-exposed mice attenuates early features of airway remodeling via a mevalonate-dependent mechanism...

Healing of burn wounds is often associated with scar formation due to excessive inflammation and delayed wound closure. To date, no effective treatment is available to prevent the fibrotic process. The Renin Angiotensin System (RAS) was shown to be involved in fibrosis in various organs. Statins (e.g. Atorvastatin), Angiotensin receptor antagonists (e.g. Losartan) and the combination of these drugs are able to reduce the local RAS activation, and reduced fibrosis in other organs. We investigated whether inhibition of the RAS could improve healing of burn wounds by treatment with Atorvastatin, Losartan or the combination of both drugs...

OBJECTIVE: Sarcopenia is a syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength, with the risk of frailty and poor quality of life. This study aimed to clarify the clinical characteristics of sarcopenia and to investigate the effects of comprehensive cardiac rehabilitation (CCR), including nutrition, physical exercise and medication, in patients with cardiovascular disease (CVD). METHODS: We retrospectively studied 322 inpatients with CVD (age 72±12 years)...

BACKGROUND: Cumulative evidence indicates that statins induce myotoxicity. However, the lack of understanding of how statins affect skeletal muscles at the structural, functional, and physiological levels hampers proper healthcare management. The purpose of the present study was to investigate the early after-effects of lovastatin on the slow-twitch soleus (Sol) and fast-twitch extensor digitorum longus (EDL) muscles. METHODS: Adult C57BL/6 mice were orally administrated with placebo or lovastatin [50 mg/kg/d] for 28 days...

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...

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...

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...

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...