ArticleJournal of clinical medicine2020
Fibrosis Distinguishes Critical Limb Ischemia Patients from Claudicants in a Transcriptomic and Histologic Analysis.
Article in Journal of clinical medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 30 citations in OpenAlex.
- Intramuscular Adipose Tissue Accumulation is a Key Determinant of Limb Function in Peripheral Artery Disease.Circulation · 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
- A smooth muscle cell lncRNA controls angiogenesis in chronic limb-threatening ischemia through miR-143-3p/HHIP signaling.The Journal of clinical investigation · 2025Article
- Multiomics Analysis of Skeletal Muscle Identifies Dysregulation of Hypoxia-Induced Genes in Peripheral Artery Disease.Journal of the American Heart Association · 2025Article
- Multiomic Analysis of Calf Muscle in Peripheral Artery Disease and Chronic Kidney Disease.Circulation research · 2025Article
- Hypoxia-induced increase in sphingomyelin synthase 2 aggravates ischemic skeletal muscle inflammation.The FEBS journal · 2025Article
- Vascular adhesion molecule 1JVS-vascular science · 2025Article
- miR-1, miR-133a, miR-29b and skeletal muscle fibrosis in chronic limb-threatening ischaemia.Scientific reports · 2024Article
- Pathological Changes in the Gastrocnemius Muscle throughout Hind Limb Ischemia Modeling in Rats.Bulletin of experimental biology and medicine · 2024Article
- Skeletal muscle regeneration failure in ischemic-damaged limbs is associated with pro-inflammatory macrophages and premature differentiation of satellite cells.Genome medicine · 2023Article
- Single-Nuclei RNA-Sequencing of the Gastrocnemius Muscle in Peripheral Artery Disease.Circulation research · 2023Article
- Transcriptomic Profiling Identifies Ferroptosis-Related Gene Signatures in Ischemic Muscle Satellite Cells Affected by Peripheral Artery Disease-Brief Report.Arteriosclerosis, thrombosis, and vascular biology · 2023Article
- Robust critical limb ischemia porcine model involving skeletal muscle necrosis.Scientific reports · 2023Article
- Transcriptomic and Proteomic of Gastrocnemius Muscle in Peripheral Artery Disease.Circulation research · 2023Article
- Multiomics Analyses of Peripheral Artery Disease Muscle Biopsies.Circulation research · 2023Article
- Subunits of C1Q Are Associated With the Progression of Intermittent Claudication to Chronic Limb-Threatening Ischemia.Frontiers in cardiovascular medicine · 2022Article
- Endothelial cell-derived pro-fibrotic factors increase TGF-β1 expression by smooth muscle cells in response to cycles of hypoxia-hyperoxia.Biochimica et biophysica acta. Molecular basis of disease · 2022Article
- Mechanisms of Xiaochaihu Decoction on Treating Hepatic Fibrosis Explored by Network Pharmacology.Disease markers · 2022Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Most patients with critical limb ischemia (CLI) from peripheral arterial disease (PAD) do not have antecedent intermittent claudication (IC). We hypothesized that transcriptomic analysis would identify CLI-specific pathways, particularly in regards to fibrosis. Derivation cohort data from muscle biopsies in PAD and non-PAD (controls) was obtained from the Gene Expression Omnibus (GSE120642). Transcriptomic analysis indicated CLI patients (N = 16) had a unique gene expression profile, when compared with non-PAD controls (N = 15) and IC (N = 20). Ninety-eight genes differed between controls and IC, 2489 genes differed between CLI and controls, and 2783 genes differed between CLI and IC patients. Pathway enrichment analysis showed that pathways associated with TGFβ, collagen deposition, and VEGF signaling were enriched in CLI but not IC. Receiver operating curve (ROC) analysis of nine fibrosis core gene expression revealed the areas under the ROC (AUC) were all >0.75 for CLI. Furthermore, the fibrosis area (AUC = 0.81) and % fibrosis (AUC = 0.87) in validation cohort validated the fibrosis discrimination CLI from IC and control (all n = 12). In conclusion, transcriptomic analysis identified fibrosis pathways, including those involving TGFβ, as a novel gene expression feature for CLI but not IC. Fibrosis is an important characteristic of CLI, which we confirmed histologically, and may be a target for novel therapies in PAD.
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