Abstract: This paper aims to synthesize current research on the pathophysiology of peripheral artery disease, identifying key biological mechanisms, molecular markers, and contributing factors to provide a comprehensive overview of the disease's underlying processes. The review utilises 100 original studies with 1005011 total participants (topic deduplicated ΣN). This scoping review comprehensively mapped the current evidence on the pathophysiology of peripheral artery disease, highlighting its intricate and multifactorial nature. A central finding across the evidence base is the pervasive role of endothelial dysfunction, driven by chronic inflammation, oxidative stress, and metabolic dysregulation, which collectively impair angiogenesis and lead to localized tissue damage. The synthesis further indicates critical involvement of mitochondrial dysfunction, genetic and environmental interactions, gut-derived metabolites, and specific molecular pathways like non-coding RNAs and extracellular vesicle signaling in disease progression. While this review provides a broad overview of the evidence landscape, the qualitative nature of its synthesis means that further rigorous studies are needed to establish causal links and validate novel biomarkers. Ultimately, understanding these diverse pathophysiological facets is crucial for developing more effective diagnostic tools and targeted therapeutic strategies for PAD patients.
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Final search date and database lock: 2026-03-09 15:12:06 CET
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Source: Semantic Scholar
Total Abstracts/Papers: 1059
Downloaded Abstracts/Papers: 1000
Included original and non-original Abstracts/Papers (all): 189
Included original Abstracts/Papers (OSMA vote counting by direction of effect): 100
Reference Index (links used in paper): 62
Total participants (topic deduplicated ΣN): 1005011
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Reference Index (62)
[2] Circulating Soluble EPCR Levels Are Reduced in Patients with Ischemic Peripheral Artery Disease and Associated with Markers of Endothelial and Vascular Function — https://doi.org/10.3390/biomedicines11092459
[7] Genome- and transcriptome-wide association meta-analysis reveals new insights into genes affecting coronary and peripheral artery disease — https://doi.org/10.1371/journal.pone.0335513
[10] Gender differences in the association between the triglyceride-glucose index and peripheral artery disease in vascular surgery inpatients aged 50 and above: a retrospective cross-sectional study — https://doi.org/10.3389/fendo.2025.1578025
[16] Abstract 11518: Incidence of Peripheral Arterial Disease in Patients With Coronary Artery Disease Following Cardiac Catheterization: A Prospective Observational Study — https://doi.org/10.1161/circ.146.suppl_1.11518
[32] Clinical management of peripheral arterial disease in chronic kidney disease—a comprehensive review from the European Renal Association CKD-MBD Working Group — https://doi.org/10.1093/ckj/sfaf089
[33] The impact of the gut microbiome on the development of atherosclerosis and peripheral arterial disease: A narrative review — https://doi.org/10.32394/pe/214773
[61] Cardiovascular events in chronic kidney disease (CKD)—an importance of vascular calcification and microcirculatory impairment — https://doi.org/10.1186/s41100-016-0062-y
[65] Activation of Nrf2 signaling: A key molecular mechanism of protection against cardiovascular diseases by natural products — https://doi.org/10.3389/fphar.2022.1057918
[69] The role of rivaroxaban for patients with atherosclerotic vascular disease in the modern era — https://doi.org/10.1002/ccd.29089
[87] Haploinsufficiency of Transferrin Receptor 1 Impairs Angiogenesis with Reduced Mitochondrial Complex I in Mice with Limb Ischemia — https://doi.org/10.1038/s41598-019-49983-4
[95] Current Opinion: Mean Platelet Volume Is One of the Most Important Parameters at the First Glance — https://doi.org/10.1159/000354738
[96] Crossroads between peripheral atherosclerosis, western-type diet and skeletal muscle pathophysiology: emphasis on apolipoprotein E deficiency and peripheral arterial disease — https://doi.org/10.1186/s12929-017-0346-8
[99] Lower-Limb Peripheral Arterial Disease and Amputations in people with Diabetes: Risk Factors, Prognostic Value and management. — https://doi.org/10.1016/j.lpm.2023.104164
[106] Oxidative stress and vascular dysfunction: Potential therapeutic targets and therapies in peripheral artery disease. — https://doi.org/10.1016/j.mvr.2024.104713
[107] Lipoprotein particle profile in the presence of peripheral artery disease among patients with coronary heart disease: Data from the CORDIOPREV study. — https://doi.org/10.1016/j.jacl.2024.12.007
[127] Evolving concepts in the pathophysiology of atherosclerosis: from endothelial dysfunction to thrombus formation through multiple shades of inflammation — https://doi.org/10.2459/jcm.0000000000001450
[131] Genetic Variants in the Bone Morphogenic Protein Gene Family Modify the Association between Residential Exposure to Traffic and Peripheral Arterial Disease — https://doi.org/10.1371/journal.pone.0152670
[141] The Association of Chronic Kidney Disease with Increased Cardiovascular Morbidity and Mortality: A Systematic Review — https://doi.org/10.70070/edv76569
[149] Gene expression profiling of peripheral blood mononuclear cells in the setting of peripheral arterial disease — https://doi.org/10.1186/2043-9113-2-6
[175] Abstract 624: Heterozygous Deletion of Transferrin Receptor 1 Impairs Angiogenesis with Reduced Mitochondrial Complex I in a Mouse Model of Hind Limb Ischemia — https://doi.org/10.1161/atvb.39.suppl_1.624
[184] Antiphospholipid antibodies in patient with acute lower member ischemia and pulmonary thromboembolism as a result of infection by SARS-CoV2 — https://doi.org/10.1007/s10067-020-05194-1
