{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T23:37:00Z","timestamp":1770680220051,"version":"3.49.0"},"reference-count":44,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2020,4,3]],"date-time":"2020-04-03T00:00:00Z","timestamp":1585872000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["FIS-PI18\/00912"],"award-info":[{"award-number":["FIS-PI18\/00912"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012818","name":"Comunidad de Madrid","doi-asserted-by":"publisher","award":["B2017\/BMD-3804 MITIC-CM"],"award-info":[{"award-number":["B2017\/BMD-3804 MITIC-CM"]}],"id":[{"id":"10.13039\/100012818","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pregnancy is a period in a woman\u2019s life associated with an increased risk of developing lower extremity chronic venous disease (CVD). Pregnancy-associated CVD is associated with changes in placental villi. We investigated angiogenesis and lymphangiogenesis in the placental villi of women with CVD during pregnancy compared with healthy controls with no history of CVD (HC). An observational, analytical, and prospective cohort study was conducted on 114 women in their third trimester of pregnancy (32 weeks). Sixty-two participants were clinically diagnosed with CVD. In parallel, 52 controls with no history of CVD (HC) were studied. Gene and protein expression of CD31, podoplanin (D2-40), Flt-1, and placental growth factor (PIGF) was analysed by real-time polymerase chain reaction (RT-qPCR) and immunohistochemistry. CD31 and D2-40 gene expression was significantly greater in the placental villi of women with CVD, as were the numbers of vessels positive for CD31 and D2-40. Significantly higher gene and protein expression of Flt-1 and PIGF was observed in the placental villi of women with CVD. Histological analysis showed more placental villi with periodic acid of Schiff (PAS)-positive material in women with CVD. Our results show a connection between pregnancy-associated CVD and leading to higher proangiogenic and lymphangiogenic activity in placental villi.<\/jats:p>","DOI":"10.3390\/ijms21072487","type":"journal-article","created":{"date-parts":[[2020,4,6]],"date-time":"2020-04-06T06:10:28Z","timestamp":1586153428000},"page":"2487","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Increased Angiogenesis and Lymphangiogenesis in the Placental Villi of Women with Chronic Venous Disease during Pregnancy"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2588-1708","authenticated-orcid":false,"given":"Miguel A","family":"Ortega","sequence":"first","affiliation":[{"name":"Department of Medicine and Medical Specialties, Faculty of Medicine and Health Sciences and Networking Biomedical Research Centre on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), University of Alcal\u00e1, 28801 Alcal\u00e1 de Henares, Madrid, Spain"},{"name":"Ram\u00f3n y Cajal Institute of Healthcare Research (IRYCIS), 28034 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8389-258X","authenticated-orcid":false,"given":"Miguel A","family":"Saez","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialties, Faculty of Medicine and Health Sciences and Networking Biomedical Research Centre on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), University of Alcal\u00e1, 28801 Alcal\u00e1 de Henares, Madrid, Spain"},{"name":"Pathological Anatomy Service, Central University Hospital of Defence-UAH Madrid, 28801 Alcal\u00e1 de Henares, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4494-6397","authenticated-orcid":false,"given":"Oscar","family":"Fraile-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialties, Faculty of Medicine and Health Sciences and Networking Biomedical Research Centre on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), University of Alcal\u00e1, 28801 Alcal\u00e1 de Henares, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7898-4685","authenticated-orcid":false,"given":"\u00c1ngel","family":"As\u00fansolo","sequence":"additional","affiliation":[{"name":"Ram\u00f3n y Cajal Institute of Healthcare Research (IRYCIS), 28034 Madrid, Spain"},{"name":"Department of Surgery, Medical and Social Sciences, Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcal\u00e1 de Henares, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonel","family":"Pekarek","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialties, Faculty of Medicine and Health Sciences and Networking Biomedical Research Centre on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), University of Alcal\u00e1, 28801 Alcal\u00e1 de Henares, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Coral","family":"Bravo","sequence":"additional","affiliation":[{"name":"Department of Surgery, Medical and Social Sciences, Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcal\u00e1 de Henares, Madrid, Spain"},{"name":"Service of Gynecology and Obstetrics, Section of Fetal Maternal Medicine, Central University Hospital of Defence-UAH Madrid, 28801 Alcal\u00e1 de Henares, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Santiago","family":"Coca","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialties, Faculty of Medicine and Health Sciences and Networking Biomedical Research Centre on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), University of Alcal\u00e1, 28801 Alcal\u00e1 de Henares, Madrid, Spain"},{"name":"Ram\u00f3n y Cajal Institute of Healthcare Research (IRYCIS), 28034 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felipe","family":"Sainz","sequence":"additional","affiliation":[{"name":"Department of Surgery, Medical and Social Sciences, Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcal\u00e1 de Henares, Madrid, Spain"},{"name":"Angiology and Vascular Surgery Service, Central University Hospital of Defence-UAH Madrid, 28801 Alcal\u00e1 de Henares, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melchor \u00c1lvarez-","family":"Mon","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialties, Faculty of Medicine and Health Sciences and Networking Biomedical Research Centre on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), University of Alcal\u00e1, 28801 Alcal\u00e1 de Henares, Madrid, Spain"},{"name":"Ram\u00f3n y Cajal Institute of Healthcare Research (IRYCIS), 28034 Madrid, Spain"},{"name":"Immune System Diseases-Rheumatology and Oncology Service, University Hospital Pr\u00edncipe de Asturias, CIBEREHD, 28801 Alcal\u00e1 de Henares, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Buj\u00e1n","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialties, Faculty of Medicine and Health Sciences and Networking Biomedical Research Centre on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), University of Alcal\u00e1, 28801 Alcal\u00e1 de Henares, Madrid, Spain"},{"name":"Ram\u00f3n y Cajal Institute of Healthcare Research (IRYCIS), 28034 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalio","family":"Garc\u00eda-Honduvilla","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialties, Faculty of Medicine and Health Sciences and Networking Biomedical Research Centre on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), University of Alcal\u00e1, 28801 Alcal\u00e1 de Henares, Madrid, Spain"},{"name":"Ram\u00f3n y Cajal Institute of Healthcare Research (IRYCIS), 28034 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"269","DOI":"10.3904\/kjim.2018.230","article-title":"Chronic venous insufficiency and varicose veins of the lower extremities","volume":"34","author":"Youn","year":"2019","journal-title":"Korean J. 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