ArticleJournal of translational medicine2016
Transforming growth factor-beta 1 produced by vascular smooth muscle cells predicts fibrosis in the gastrocnemius of patients with peripheral artery disease.
Article in Journal of translational medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- Sarcopenia and peripheral arterial disease: a systematic review.Journal of cachexia, sarcopenia and muscle · 2020Pooled it
- SIRT6 alleviates ischemic injury via orchestrating the RREB1/Snail and STC1/Smad7 signaling pathways to regulate endothelial-mesenchymal transition.Science China. Life sciences · 2026Article
- Intramuscular Adipose Tissue Accumulation is a Key Determinant of Limb Function in Peripheral Artery Disease.Circulation · 2026Article
- A Cross-sectional Study on Age-Related Changes in Muscle Iron Deposition and Fat Infiltration: Associations with Grip Strength in a Healthy Adult Cohort.Biological trace element research · 2026Article
- Intramuscular Adipose Tissue Accumulation is a Key Determinant of Limb Function in Peripheral Artery Disease.bioRxiv : the preprint server for biology · 2026Article
- Profiling of main regulators of angiogenesis and inflammation in human PBMC and plasma revealed associations with lower extremity artery disease.Scientific reports · 2025Article
- Pirfenidone treatment improves ischemic muscle function in mice with chronic kidney disease.Skeletal muscle · 2025Article
- Deciphering the Role of Ferroptosis in the Pathogenesis of Peripheral Artery Disease Myopathy.Biology · 2025Article
- Multiomic Analysis of Calf Muscle in Peripheral Artery Disease and Chronic Kidney Disease.Circulation research · 2025Article
- Telmisartan modulates exercise responses in peripheral artery disease: Analyses of skeletal muscle from the TELEX Trial.JVS-vascular science · 2025Article
- Molecular Pathophysiology of Chronic Thromboembolic Pulmonary Hypertension: A Clinical Update from a Basic Research Perspective.Advances in respiratory medicine · 2024Review
- miR-1, miR-133a, miR-29b and skeletal muscle fibrosis in chronic limb-threatening ischaemia.Scientific reports · 2024Article
- Endothelial-to-Mesenchymal Transition in Cardiovascular Pathophysiology.International journal of molecular sciences · 2024Review
- Oxidative damage in the gastrocnemius predicts long-term survival in patients with peripheral artery disease.npj aging · 2024Article
- Hybrid ultrasound and single wavelength optoacoustic imaging reveals muscle degeneration in peripheral artery disease.Photoacoustics · 2024Article
- Single-Nuclei RNA-Sequencing of the Gastrocnemius Muscle in Peripheral Artery Disease.Circulation research · 2023Article
- Using T1 mapping indices to evaluate muscle function and predict conservative treatment outcomes in diabetic patients with peripheral arterial disease.European radiology · 2023Article
- Transcriptomic and Proteomic of Gastrocnemius Muscle in Peripheral Artery Disease.Circulation research · 2023Article
- Diabetes mellitus in peripheral artery disease: Beyond a risk factor.Frontiers in cardiovascular medicine · 2023Review
- Impaired microcirculatory function, mitochondrial respiration, and oxygen utilization in skeletal muscle of claudicating patients with peripheral artery disease.American journal of physiology. Heart and circulatory physiology · 2022Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundLower leg ischemia, myopathy, and limb dysfunction are distinguishing features of peripheral artery disease (PAD). The myopathy of PAD is characterized by myofiber degeneration in association with extracellular matrix expansion, and increased expression of transforming growth factor-beta 1 (TGF-β1; a pro-fibrotic cytokine). In this study, we evaluated cellular expression of TGF-β1 in gastrocnemius of control (CTRL) and PAD patients and its relationship to deposited collagen, fibroblast accumulation and limb hemodynamics.
methodsGastrocnemius biopsies were collected from PAD patients with claudication (PAD-II; N = 25) and tissue loss (PAD-IV; N = 20) and from CTRL patients (N = 20). TGF-β1 in slide-mounted specimens was labeled with fluorescent antibodies and analyzed by quantitative wide-field, fluorescence microscopy. We evaluated co-localization of TGF-β1 with vascular smooth muscle cells (SMC) (high molecular weight caldesmon), fibroblasts (TE-7 antigen), macrophages (CD163), T cells (CD3) and endothelial cells (CD31). Collagen was stained with Masson Trichrome and collagen density was determined by quantitative bright-field microscopy with multi-spectral imaging.
resultsCollagen density increased from CTRL to PAD-II to PAD-IV specimens (all differences p < 0.05) and was prominent around microvessels. TGF-β1 expression increased with advancing disease (all differences p < 0.05), correlated with collagen density across all specimens (r = 0.864; p < 0.001), associated with fibroblast accumulation, and was observed exclusively in SMC. TGF-β1 expression inversely correlated with ankle-brachial index across PAD patients (r = -0.698; p < 0.001).
conclusionsOur findings support a progressive fibrosis in the gastrocnemius of PAD patients that is caused by elevated TGF-β1 production in the SMC of microvessels in response to tissue hypoxia.
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