ArticleCirculation research2023
Transcriptomic and Proteomic of Gastrocnemius Muscle in Peripheral Artery Disease.
Article in Circulation research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 40 citations in OpenAlex.
- Nicotinamide riboside for peripheral artery disease: the NICE randomized clinical trial.Nature communications · 2024Trial
- The Role of Home-Based Exercise in the Management of Peripheral Artery Disease.Current treatment options in cardiovascular medicine · 2026Article
- A cardiovascular-motor axis framework for perfusion-mediated motor impairment.International journal of cardiology. Heart & vasculature · 2026Review
- Cilostazol use and calf muscle pathophysiology in people with peripheral artery disease.Vascular medicine (London, England) · 2026Article
- Disrupted Mitochondrial Quality Control in Atherosclerotic Disease: Mitophagy and Dynamics in Focus.JACC. Basic to translational science · 2026Review
- Exercise-associated microbial metabolites prevent skeletal muscle atrophy in adult female mice.Nature communications · 2026Article
- Mitochondrial quality control in human ageing and longevity.Nature metabolism · 2026Review
- Variant-to-Biomarker Pathways in Peripheral Artery Disease: Multiomics Integration and Clinical Translation.Human mutation · 2026Review
- Age-related decline of chaperone-mediated autophagy in skeletal muscle leads to progressive myopathy.Nature metabolism · 2025Article
- Genetic Insights into Peripheral Artery Disease: A Narrative Review.Biomedicines · 2025Review
- Multiomics Analysis of Skeletal Muscle Identifies Dysregulation of Hypoxia-Induced Genes in Peripheral Artery Disease.Journal of the American Heart Association · 2025Article
- Single-cell compendium of muscle microenvironment in peripheral artery disease reveals altered endothelial diversity and LYVE1Nature cardiovascular research · 2025Article
- In-vitro human myogenesis model reveals novel mRNA alternative splicing isoforms.Scientific reports · 2025Article
- Nicotinamide N-methyltransferase inhibition improves limb function in experimental peripheral artery disease.Physiological reports · 2025Article
- SomaModules: A Pathway Enrichment Approach Tailored to SomaScan Data.Journal of proteome research · 2025Article
- Article
- Myocardial mitochondrial antiviral signaling protein promotes heart Ischemia-reperfusion injury via RIG-I signaling in mice.Nature communications · 2025Article
- Multiomic Analysis of Calf Muscle in Peripheral Artery Disease and Chronic Kidney Disease.Circulation research · 2025Article
- Pathophysiological insights into HFpEF from studies of human cardiac tissue.Nature reviews. Cardiology · 2025Review
- Proteomic Profiling Towards a Better Understanding of Genetic Based Muscular Diseases: The Current Picture and a Look to the Future.Biomolecules · 2025Review
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundFew effective therapies exist to improve lower extremity muscle pathology and mobility loss due to peripheral artery disease (PAD), in part because mechanisms associated with functional impairment remain unclear.
methodsTo better understand mechanisms of muscle impairment in PAD, we performed in-depth transcriptomic and proteomic analyses on gastrocnemius muscle biopsies from 31 PAD participants (mean age, 69.9 years) and 29 age- and sex-matched non-PAD controls (mean age, 70.0 years) free of diabetes or limb-threatening ischemia.
resultsTranscriptomic and proteomic analyses suggested activation of hypoxia-compensatory mechanisms in PAD muscle, including inflammation, fibrosis, apoptosis, angiogenesis, unfolded protein response, and nerve and muscle repair. Stoichiometric proportions of mitochondrial respiratory proteins were aberrant in PAD compared to non-PAD, suggesting that respiratory proteins not in complete functional units are not removed by mitophagy, likely contributing to abnormal mitochondrial activity. Supporting this hypothesis, greater mitochondrial respiratory protein abundance was significantly associated with greater complex II and complex IV respiratory activity in non-PAD but not in PAD. Rate-limiting glycolytic enzymes, such as hexokinase and pyruvate kinase, were less abundant in muscle of people with PAD compared with non-PAD participants, suggesting diminished glucose metabolism.
conclusionsIn PAD muscle, hypoxia induces accumulation of mitochondria respiratory proteins, reduced activity of rate-limiting glycolytic enzymes, and an enhanced integrated stress response that modulates protein translation. These mechanisms may serve as targets for disease modification.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.