Chronic kidney disease (CKD) leads to increased skeletal muscle fatigue, weakness, and atrophy. Previous work has implicated mitochondria within the as a mediator of dysfunction in CKD; however, mechanisms underlying mitochondrial CKD are not entirely known. The purpose this study was define impact uremic metabolites on energetics. Skeletal were isolated from C57BL/6N mice exposed vehicle (DMSO) or varying concentrations metabolites: indoxyl sulfate, indole-3-acetic-acid, l-kynurenine,...

Preclinical models of chronic kidney disease (CKD) are critical to investigate the mechanisms and evaluate novel therapeutics aimed treat CKD-associated pathologies. The objective present study was compare adenine diet 5/6 nephrectomy (5/6 Nx) in mice. Male female 10-week-old C57BL/6J mice (N=5-9/sex/group) were randomly allocated CKD groups (0.2-0.15% adenine-supplemented or Nx surgery) corresponding control (casein sham surgery). Glomerular filtration rate reduced a similar level (adenine...

BACKGROUND: Chronic kidney disease (CKD) has emerged as a significant risk factor that accelerates atherosclerosis, decreases muscle function, and increases the of amputation or death in patients with peripheral artery (PAD). However, modulators underlying this exacerbated pathobiology are ill-defined. Recent work demonstrated uremic toxins associated limb PAD have pathological effects both vasculature. Herein, we use multiomics to identify novel CKD. METHODS: A cross-sectional study...

Chronic kidney disease (CKD) causes progressive skeletal myopathy involving atrophy, weakness, and fatigue. Mitochondria have been thought to contribute myopathy; however, the molecular mechanisms underlying muscle metabolism changes in CKD are unknown. We employed a comprehensive mitochondrial phenotyping platform elucidate of impairment mice with adenine-induced CKD. displayed significant reductions oxidative phosphorylation (OXPHOS), which was strongly correlated glomerular filtration...

Abstract Background Accumulating evidence has demonstrated that chronic tobacco smoking directly contributes to skeletal muscle dysfunction independent of its pathological impact the cardiorespiratory systems. The mechanisms underlying smoke toxicity in are not fully resolved. In this study, role aryl hydrocarbon receptor (AHR), a transcription factor known be activated with smoke, was investigated. Methods AHR related gene (mRNA) expression quantified from adult controls and patients...

Lower extremity peripheral artery disease (PAD) is a growing epidemic with limited effective treatment options. Here, we provide single-nuclei atlas of PAD limb muscle to facilitate better understanding the composition cells and transcriptional differences that comprise diseased muscle.

Lower-extremity peripheral arterial disease (PAD) has increased in prevalence, yet therapeutic development remained stagnant. Skeletal muscle health and function been strongly linked to quality of life medical outcomes patients with PAD. Using a rodent model PAD, this study demonstrates that treatment the ischemic limb insulin-like growth factor (IGF)-1 significantly increases size strength without improving hemodynamics. Interestingly, effect IGF1 therapy was larger female mice than male...

Abstract Chronic kidney disease (CKD) substantially increases the severity of peripheral arterial (PAD) symptomology, however, biological mechanisms remain unclear. The objective herein was to determine impact CKD on PAD pathology in mice. C57BL6/J mice were subjected a diet-induced model by delivery adenine for six weeks. confirmed measurements glomerular filtration rate, blood urea nitrogen, and histopathology. Mice with displayed lower muscle force production greater ischemic lesions...

Chronic kidney disease (CKD) results in the impaired filtration of metabolites, which may be toxic or harmful to organs/tissues. The objective this study was perform unbiased 1H nuclear magnetic resonance (NMR)-based metabolomics profiling tissues from mice with CKD. Five-month-old male C57BL6J were placed on either a casein control diet adenine-supplemented induce CKD for 24 weeks. confirmed by significant increases blood urea nitrogen (24.1 ± 7.7 vs. 105.3 18.3 mg/dL, p < 0.0001)...

Chronic kidney disease (CKD) accelerates the development of atherosclerosis, decreases muscle function, and increases risk amputation or death in patients with peripheral artery (PAD). However, mechanisms underlying this pathobiology are ill-defined. Recent work has indicated that tryptophan-derived uremic solutes, which ligands for AHR (aryl hydrocarbon receptor), associated limb PAD. Herein, we examined role activation myopathy PAD CKD.

Chronic kidney disease (CKD) causes accumulation of uremic metabolites that negatively affect skeletal muscle. Tryptophan-derived are agonists the aryl hydrocarbon receptor (AHR), which has been shown to be activated in CKD. This study investigated role AHR muscle pathology Compared with controls normal function, AHR-dependent gene expression (CYP1A1 and CYP1B1) was significantly upregulated patients CKD, magnitude activation inversely correlated mitochondrial respiration. In mice oxidative...

Chronic limb threatening ischemia (CLTI) is the most severe manifestation of peripheral atherosclerosis. Patients with CLTI have poor muscle quality and function are at high risk for amputation death. The objective this study was to interrogate metabolome from patients. To accomplish this, a prospective cohort patients undergoing either surgical intervention (CLTI Pre-surgery) or Amputation), as well non-peripheral arterial disease (non-PAD) controls were enrolled. Gastrocnemius biopsy...

Chronic kidney disease (CKD) results in reduced function, uremia, and accumulation of uremic metabolites. Mitochondrial alterations have been suggested to play a role the pathology within various tissues. The purpose this study was perform comprehensive bioenergetic proteomic phenotyping mitochondria from skeletal muscle (SkM), cardiac (CM), renal tissue mice with CKD. 5-month-old C57BL/6J male were fed casein control or adenine-supplemented diet for 6 months. CKD confirmed by blood urea...

The objective of the present study was to determine whether elevated levels S100A8 and S100A9 (S100A8/A9) alarmins contribute ischemic limb pathology.Gastrocnemius muscle collected from control patients without peripheral arterial disease (PAD; n = 14) with chronic threatening ischemia (CLTI; 14). Mitochondrial function assessed in permeabilized fibers, RNA protein analyses were used quantify S100A8/A9 levels. Additionally, a mouse model hindlimb exogenous delivery used.Compared non-PAD...

Introduction: L-Kynurenine (L-Kyn), a product of tryptophan (Trp) catabolism, has been linked with impairments in walking speed, muscle strength/size, and physical function. The purpose this pilot study was to develop dietary model that elevates plasma L-Kyn levels mice characterize its impact on health Methods: Four-month-old C57BL6J male were randomized either supplemented (150 mg/kg) or chow diet for 10 weeks. Plasma Trp measured via mass spectrometry. Primary outcomes included...

Tobacco smoke-related diseases such as chronic obstructive pulmonary disease (COPD) are associated with high healthcare burden and mortality rates. Many COPD patients were reported to have muscle atrophy weakness, several studies suggesting intrinsic mitochondrial impairment a possible driver of this phenotype. Whereas much information has been learned about pathology once patient COPD, little is known how active tobacco smoking might impact skeletal physiology or health. In study, we...

The effect of exertional heat stroke (EHS) exposure on skeletal muscles is incompletely understood. Muscle weakness an early symptom EHS but not considered a major target multiorgan injury. Previously, in preclinical mouse model EHS, we observed the vulnerability limb to second exposure, suggesting hidden processes contributing declines muscle resilience. Here, evaluated possible molecular origins EHS-induced Female C57BL/6 mice [total

BACKGROUND: Chronic kidney disease (CKD) has emerged as a significant risk factor that accelerates atherosclerosis, decreases muscle function, and increases the of amputation or death in patients with peripheral artery (PAD). However, modulators underlying this exacerbated pathobiology are ill-defined. Recent work demonstrated uremic toxins associated limb PAD have pathological effects both vasculature. Herein, we utilize multiomics to identify novel CKD. METHODS: A cross-sectional study...

Cardiomyocyte dysfunction in patients with end-stage heart failure reduced ejection fraction (HFrEF) stems from mitochondrial dysfunction, which contributes to an energetic crisis. Mitochondrial reportedly relates increased markers of oxidative stress, but the impact reversible thiol oxidation on myocardial function HFrEF has not been investigated. In present study, we assessed ventricular biopsies presence and absence thiol-reducing agent dithiothreitol (DTT). Isolated mitochondria exposed...

CONDENSED ABSTRACT Lower extremity peripheral arterial disease (PAD) has continued to increase in prevalence over the past several decades, yet therapeutic development remained stagnant. Skeletal muscle health and function been strongly linked quality of life medical outcomes PAD patients. Using a rodent model PAD, this study demonstrates that treatment ischemic limb with adeno-associated virus-mediated expression insulin-like growth factor 1 (IGF1) significantly increases size strength,...

Introduction: Peripheral artery disease (PAD) affects approximately 200 million people globally. Chronic limb-threatening ischemia (CLTI) represents the most advanced clinical phenotype of PAD. Mitochondrial metabolism defects are apparent in satellite cells CLTI patients, and muscle regeneration process demands increased energy, with cell mitochondrial dynamics playing a crucial role. However, our current understanding role PAD pathology is notably inadequate. Recent studies have shown that...

Introduction: Chronic kidney disease is a significant risk factor for both the development of peripheral artery (PAD) and major adverse limb events. However, little known about how coalescence these two conditions impacts muscle pathophysiology. The objective current study was to determine impact CKD on skeletal strength mitochondrial health in patients with without PAD. Methods: A cross-sectional prospective design employed assess plantar flexor strength, fiber area (CSA), four groups (61...