{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T19:05:02Z","timestamp":1776625502213,"version":"3.51.2"},"reference-count":41,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2012,1]]},"abstract":"<jats:p> Angiopoietin (Ang)-2, a ligand of the receptor tyrosine kinase Tie2, is known to be involved in the regulation of embryonic lymphangiogenesis. However, the role of Ang-2 in postnatal pathological lymphangiogenesis, such as inflammation, is largely unknown. We used a combination of imaging, molecular, and cellular approaches to investigate whether Ang-2 is involved in inflammatory lymphangiogenesis. We observed strong and continuous expression of Ang-2 on newly generated lymphatic vessels for 2 wk in sutured corneas of BALB\/c mice. This expression was concurrent with an increased number of lymphatic vessels. TNF-\u03b1 expression also increased, with peak TNF-\u03b1 expression occurring before peak Ang-2 expression was reached. In vitro experiments showed that TNF-\u03b1 stimulates Ang-2 and Tie2 and ICAM-1 expression on human lymphatic endothelial cells (LECs) and blood vascular endothelial cells (BECs). Ang-2 alone did not affect the biological behavior of LECs, whereas Ang-2 combined with TNF-\u03b1 significantly promoted the proliferation of LECs but not BECs. In mouse models, blockade of Ang-2 with L1-10, an Ang-2-specific inhibitor, significantly inhibited lymphangiogenesis but promoted angiogenesis. These results clearly indicate that Ang-2 acts as a crucial regulator of inflammatory lymphangiogenesis by sensitizing the lymphatic vasculature to inflammatory stimuli, thereby directly promoting lymphangiogenesis. The involvement of Ang-2 in inflammatory lymphangiogenesis provides a strong rationale for the exploitation of anti-Ang-2 treatment in the prevention and treatment of tumor metastasis and transplant rejection. <\/jats:p>","DOI":"10.1152\/ajpheart.00895.2011","type":"journal-article","created":{"date-parts":[[2011,11,5]],"date-time":"2011-11-05T00:32:55Z","timestamp":1320453175000},"page":"H215-H223","source":"Crossref","is-referenced-by-count":29,"title":["Angiopoietin-2 promotes inflammatory lymphangiogenesis and its effect can be blocked by the specific inhibitor L1-10"],"prefix":"10.1152","volume":"302","author":[{"given":"Zhi-Xin","family":"Yan","sequence":"first","affiliation":[{"name":"Lymphology Center, Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital and Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhao-Hua","family":"Jiang","sequence":"additional","affiliation":[{"name":"Lymphology Center, Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital and Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ning-Fei","family":"Liu","sequence":"additional","affiliation":[{"name":"Lymphology Center, Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital and Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/s00384-008-0622-x"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.11.040193.004003"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.06-0570"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s00417-007-0683-5"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1126\/science.1071924"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1172\/JCI20465"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1097\/01.ico.0000183485.85636.ff"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.03-0940"},{"key":"B9","first-page":"2127","volume":"43","author":"Cursiefen C","year":"2002","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1007\/s11596-007-0103-4"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2007.060896"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/nm1351"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-10-3685"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(02)00217-4"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.21150"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1002\/art.24764"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1089\/lrb.2006.4403"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.cryobiol.2009.10.009"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600763"},{"key":"B20","first-page":"1786","volume":"61","author":"Karpanen T","year":"2001","journal-title":"Cancer Res"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-09-176776"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/nm1340"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"B24","first-page":"3735","volume":"27","author":"Maekawa S","year":"2007","journal-title":"Anticancer Res"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5322.55"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1089\/152308604322899314"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.22.15732"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2004.09.030"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65021-3"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/dji003"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.01653"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.2741\/3066"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-008-0513-9"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-006-0360-8"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1038\/84643"},{"key":"B36","first-page":"413","volume":"37","author":"Streilein JW","year":"1996","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00400.2008"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(00)00231-5"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.108.175463"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0802486105"},{"key":"B41","first-page":"3403","volume":"63","author":"Zhang L","year":"2003","journal-title":"Cancer Res"}],"container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpheart.00895.2011","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,8]],"date-time":"2019-09-08T22:22:54Z","timestamp":1567981374000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpheart.00895.2011"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,1]]},"references-count":41,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2012,1]]}},"alternative-id":["10.1152\/ajpheart.00895.2011"],"URL":"https:\/\/doi.org\/10.1152\/ajpheart.00895.2011","relation":{},"ISSN":["0363-6135","1522-1539"],"issn-type":[{"value":"0363-6135","type":"print"},{"value":"1522-1539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,1]]}}}