{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T11:14:48Z","timestamp":1773400488814,"version":"3.50.1"},"reference-count":88,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T00:00:00Z","timestamp":1757376000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical University of Lublin","award":["PBsd40"],"award-info":[{"award-number":["PBsd40"]}]},{"name":"Medical University of Lublin","award":["DS43"],"award-info":[{"award-number":["DS43"]}]},{"name":"statutory funds of the Medical University of Lublin","award":["PBsd40"],"award-info":[{"award-number":["PBsd40"]}]},{"name":"statutory funds of the Medical University of Lublin","award":["DS43"],"award-info":[{"award-number":["DS43"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Lower extremity artery disease (LEAD), abdominal aortic aneurysm (AAA), and varicose veins (VV) are frequently underdiagnosed and undertreated peripheral vascular diseases that pose considerable public health challenges. More research is required to elucidate the pathophysiological mechanisms underlying these conditions and to identify novel diagnostic and therapeutic biomarkers. Therefore, in our study, we aimed to identify shared and distinct pathways associated with angiogenesis and inflammation in LEAD, AAA, and VV. The expression of 18 genes in peripheral blood mononuclear cells and the plasma levels of six proteins were compared between groups of 40 patients with LEAD, 40 patients with AAA, and 40 patients with VV. Independent RNA-seq and microRNA-seq data were integrated to predict differentially expressed transcription factors and microRNAs associated with the most significant genes. Gene Ontology functional analysis was performed to determine the potential biological effects of the observed dysregulations. The elevated expression of VEGFB and TGFB1, along with increased plasma levels of VEGF-C and reduced plasma levels of VEGF-A, were distinguishing features of patients with LEAD compared to those with AAA and VV. Decreased plasma levels of TGF-alpha and TGF-beta 1 were found to be indicative of varicose veins compared to individuals with arterial diseases (LEAD and AAA). Transcription factors and microRNAs potentially regulating the obtained signatures were identified and integrated into a hypothetical regulatory network. The observed dysregulations were found to be functionally associated with the response to hypoxia, the positive regulation of angiogenesis, chemotaxis, vascular permeability, and cell adhesion. The presented study identified dysregulations of key angiogenesis- and inflammation-related factors in peripheral blood mononuclear cells and plasma between LEAD, AAA, and VV patients, providing new insights into the shared and distinct molecular mechanisms underlying these diseases.<\/jats:p>","DOI":"10.3390\/ijms26188786","type":"journal-article","created":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T10:27:12Z","timestamp":1757500032000},"page":"8786","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Molecular Signatures Related to Inflammation and Angiogenesis in Patients with Lower Extremity Artery Disease, Abdominal Aortic Aneurysm, and Varicose Veins: Shared and Distinct Pathways"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2254-2009","authenticated-orcid":false,"given":"Daniel","family":"Zalewski","sequence":"first","affiliation":[{"name":"Chair and Department of Biology and Genetics, Medical University of Lublin, 4a Chod\u017aki St., 20-093 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8185-4088","authenticated-orcid":false,"given":"Paulina","family":"Chmiel","sequence":"additional","affiliation":[{"name":"Randox Laboratories Ltd., Pozna\u0144ska St., 00-680 Warszawa, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3710-0860","authenticated-orcid":false,"given":"Przemys\u0142aw","family":"Ko\u0142odziej","sequence":"additional","affiliation":[{"name":"Chair and Department of Biology and Genetics, Medical University of Lublin, 4a Chod\u017aki St., 20-093 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7406-1728","authenticated-orcid":false,"given":"Marcin","family":"Feldo","sequence":"additional","affiliation":[{"name":"Chair and Department of Vascular Surgery and Angiology, Medical University of Lublin, 11 Staszica St., 20-081 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrzej","family":"St\u0119pniewski","sequence":"additional","affiliation":[{"name":"ECOTECH-COMPLEX Analytical and Programme Centre for Advanced Environmentally Friendly Technologies, University of Marie Curie-Sk\u0142odowska, 39 G\u0142\u0119boka St., 20-612 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4039-9522","authenticated-orcid":false,"given":"Marta","family":"Ziaja-So\u0142tys","sequence":"additional","affiliation":[{"name":"Chair and Department of Biology and Genetics, Medical University of Lublin, 4a Chod\u017aki St., 20-093 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5459-4995","authenticated-orcid":false,"given":"Joanna","family":"\u0141uszczak","sequence":"additional","affiliation":[{"name":"Chair and Department of Biology and Genetics, Medical University of Lublin, 4a Chod\u017aki St., 20-093 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6939-9898","authenticated-orcid":false,"given":"Agata","family":"Stanek","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Metabolic Diseases and Angiology, Faculty of Health Sciences in Katowice, Medical University of Silesia, Zio\u0142owa 45\/47 St., 40-635 Katowice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9541-6353","authenticated-orcid":false,"given":"Janusz","family":"Kocki","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Chair of Medical Genetics, Medical University of Lublin, 11 Radziwi\u0142\u0142owska St., 20-080 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8473-7429","authenticated-orcid":false,"given":"Anna","family":"Bogucka-Kocka","sequence":"additional","affiliation":[{"name":"Chair and Department of Biology and Genetics, Medical University of Lublin, 4a Chod\u017aki St., 20-093 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e171","DOI":"10.1161\/CIR.0000000000001005","article-title":"Lower Extremity Peripheral Artery Disease: Contemporary Epidemiology, Management Gaps, and Future Directions: A Scientific Statement From the American Heart Association","volume":"144","author":"Criqui","year":"2021","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/s41569-021-00607-3","article-title":"Epidemiology of Cardiovascular Disease in Europe","volume":"19","author":"Townsend","year":"2022","journal-title":"Nat. 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