{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T19:13:27Z","timestamp":1777922007817,"version":"3.51.4"},"reference-count":36,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2011,9,1]],"date-time":"2011-09-01T00:00:00Z","timestamp":1314835200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Lymphatic Research and Biology"],"published-print":{"date-parts":[[2011,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Lymphedema is the progressive distention of tissue due to lymphatic dysfunction. The affected area enlarges over time because of fibroadipose deposition, causing morbidity. Because increasing tissue mass requires neovascularization, we hypothesized that angiogenesis or vasculogenesis might be upregulated in lymphedema.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results:<\/jats:title>\n                    <jats:p>\n                      Lymphedematous tissue was collected prospectively from nine patients after resection: upper extremity (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      =1), lower extremity (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      =3), penis\/scrotum (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      =5). Neovascularization was compared to normal tissue. Specimens were analyzed using immunohistochemistry for \u03b1-smooth muscle actin (pericyte marker), CD31 (microvascular density), CD31\/Ki67 (proliferating endothelial cells), and CD34\/CD133 (endothelial progenitor cells). Quantitative real-time PCR (qRT-PCR) was used to determine mRNA expression of progenitor cells (CD133) and factors that recruit them: vascular endothelial growth factor-A (VEGF-A), hypoxia-inducible factor 1\u03b1 (HIF-1\u03b1), matrix metalloproteinase-9 (MMP-9), and stromal-cell derived factor 1\u03b1 (SDF-1\u03b1). Angiopoetin-1,-2 (ANG-1,-2), matrix metalloproteinase-2 (MMP-2), and VEGF receptors (VEGFR1,2) were quantified using qRT-PCR. There was no difference in microvascular density, pericytic density, or endothelial proliferation between lymphedematous and normal tissue (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      =0.1). Endothelial progenitor cells were not present in lymphedema or normal specimens (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      &lt;0.01). VEGF-A (1.3-fold), HIF-1\u03b1 (0.8-fold), SDF-1\u03b1 (2.1-fold), VEGFR2 (0.09-fold), and CD133 (0.02-fold) expression were not elevated compared to normal tissue (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      =0.1). ANG-1 (5.6-fold), ANG-2 (2.5-fold), MMP-2 (3.9-fold), MMP-9 (33.4-fold), and VEGFR1 (12.8-fold) mRNA was increased in lymphedematous specimens compared to control (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      &lt;0.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Lymphedematous tissue does not exhibit upregulation of angiogenesis or vasculogenesis. Neovascularization is unlikely to be involved in the pathogenesis of this disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/lrb.2011.0008","type":"journal-article","created":{"date-parts":[[2011,11,8]],"date-time":"2011-11-08T12:09:56Z","timestamp":1320754196000},"page":"143-149","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":9,"title":["Expression of Angiogenic and Vasculogenic Factors in Human Lymphedematous Tissue"],"prefix":"10.1177","volume":"9","author":[{"given":"Rafael A.","family":"Couto","sequence":"first","affiliation":[{"name":"Harvard Medical School"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ann M.","family":"Kulungowski","sequence":"additional","affiliation":[{"name":"Harvard Medical School"},{"name":"Harvard Medical School"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aditya S.","family":"Chawla","sequence":"additional","affiliation":[{"name":"Harvard Medical School"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven J.","family":"Fishman","sequence":"additional","affiliation":[{"name":"Harvard Medical School"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arin K.","family":"Greene","sequence":"additional","affiliation":[{"name":"Harvard Medical School"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2011,11,8]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1089\/lrb.2008.1022"},{"key":"e_1_3_3_3_2","first-page":"3","article-title":"Lymphatic filiriasis. Fourth report of the WHO Expert Committee on Filiriasis","volume":"702","author":"WHO ECR","year":"1984","unstructured":"WHO ECR. Lymphatic filiriasis. Fourth report of the WHO Expert Committee on Filiriasis. World Health Organ Tech Rep Ser., 1984; 702:3\u2013112.","journal-title":"World Health Organ Tech Rep Ser."},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0954-6820.1950.tb13188.x"},{"key":"e_1_3_3_5_2","first-page":"263","article-title":"Genetic and physiologic studies of Milroy's disease","volume":"7","author":"Easterly J","year":"1959","unstructured":"Easterly J, , McKusick V. Genetic and physiologic studies of Milroy's disease. 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