{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T10:54:59Z","timestamp":1775472899787,"version":"3.50.1"},"reference-count":55,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2018,5,17]],"date-time":"2018-05-17T00:00:00Z","timestamp":1526515200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Beijing Innovation Promoting Project","award":["TJSHG201510025005"],"award-info":[{"award-number":["TJSHG201510025005"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation","doi-asserted-by":"crossref","award":["81 370 339"],"award-info":[{"award-number":["81 370 339"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation","doi-asserted-by":"crossref","award":["81 570 206"],"award-info":[{"award-number":["81 570 206"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Diabetes"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Diabetes mellitus (DM) complications are associated with ischemic injury. Angiogenesis is a therapeutic strategy for diabetic foot. The aim of this study was to investigate the possible angiogenic effect of low molecular weight fucoidan (LMWF) in diabetic peripheral arterial disease (PAD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Diabetic <jats:italic>db\/db<\/jats:italic> mice and age\u2010matched C57BL\/6 mice underwent femoral artery ligation followed by LMWF (30, 60, 80\u2009mg\/kg per day, p.o.) or cilostazol (30\u2009mg\/kg\/day, p.o.) treatment for 6\u2009weeks. Endothelium\u2010dependent vasodilation and blood flow of the hindlimb were measured. Histological and western blot analyses of CD34, vascular endothelial growth factor (VEGF), eNOS, and inflammatory factors in the gastrocnemius were performed. The effects of LMWF were confirmed in human umbilical vein endothelial cells (HUVEC).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Diabetic mice with ligation exhibited hindlimb ulceration, hydrosarca, and necrosis, increased expression of inflammatory factors, and decreased levels of VEGF and eNOS phosphorylation. Treatment with LMWF markedly ameliorated foot lesions, suppressed expression of inflammatory factors, and improved plantar perfusion by promoting endothelium\u2010dependent vasodilation and revascularization in diabetic PAD mice. In high\u2010glucose treated HUVEC, LMWF (40\u2009\u03bcg\/mL) reversed blunted endothelial cell proliferation, migration, and tube formation, and promoted eNOS phosphorylation and VEGF expression, whereas HUVEC pretreatment with 100\u2009\u03bcmol\/L <jats:italic>N<\/jats:italic><jats:sup>G<\/jats:sup>\u2010nitro\u2010<jats:sc>l<\/jats:sc>\u2010arginine methyl ester, an eNOS antagonist, markedly inhibited the effects of LMWF.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study demonstrates that LMWF alleviates hindlimb ischemic damage, at least in part by promoting eNOS phosphorylation, nitric oxide production, and VEGF expression, resulting in enhanced angiogenesis in the ischemic region.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1753-0407.12667","type":"journal-article","created":{"date-parts":[[2018,4,10]],"date-time":"2018-04-10T00:55:53Z","timestamp":1523321753000},"page":"820-834","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Low molecular\u2010weight fucoidan protects against hindlimb ischemic injury in type 2 diabetic mice through enhancing endothelial nitric oxide synthase phosphorylation"],"prefix":"10.1111","volume":"10","author":[{"given":"Tiantian","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Beijing Key Laboratory of Cardiovascular Diseases Related to Metabolic Disturbance Capital Medical University  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiqiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Beijing Key Laboratory of Cardiovascular Diseases Related to Metabolic Disturbance Capital Medical University  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoping","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Beijing Key Laboratory of Cardiovascular Diseases Related to Metabolic Disturbance Capital Medical University  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongjie","family":"You","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Beijing Key Laboratory of Cardiovascular Diseases Related to Metabolic Disturbance Capital Medical University  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingyi","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Beijing Key Laboratory of Cardiovascular Diseases Related to Metabolic Disturbance Capital Medical University  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dayong","family":"Cai","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanyuan","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Beijing Key Laboratory of Cardiovascular Diseases Related to Metabolic Disturbance Capital Medical University  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Beijing Key Laboratory of Cardiovascular Diseases Related to Metabolic Disturbance Capital Medical University  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dali","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Beijing Key Laboratory of Cardiovascular Diseases Related to Metabolic Disturbance Capital Medical University  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,5,17]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2008.10.015"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.4239\/wjd.v2.i6.92"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/1753-0407.12474"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3767"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2008.00319.x"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.107.727347"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.1995"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2014.12"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2016.06.054"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2010.02.011"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10517-007-0226-4"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2011.05.009"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.carbpol.2013.10.019"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.carbpol.2012.09.066"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fitote.2012.09.014"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2011.05.022"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2011.04554.x"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.102.046144"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2017.09.014"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2009.185"},{"key":"e_1_2_7_22_1","volume-title":"Guide for the Care and Use of Laboratory Animals","author":"National Research Council","year":"1996"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2012.08.012"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2009.10.015"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0044476"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2006.02.048"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.2176\/nmc.52.516"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2018.03.015"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1159\/000355825"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2013.09.006"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/1753-0407.12521"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2009.01.038"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.1973"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1089\/wound.2013.0517"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2008.03.026"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc07-1421"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.burns.2011.03.020"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.107.160630"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0897-879"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0704956"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2010.03.020"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/21224"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-009-0767-7"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2013.08.006"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.309326"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2013.00347"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-017-0531-9"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.111.189498"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vph.2014.06.004"},{"key":"e_1_2_7_50_1","first-page":"453","article-title":"Requirements for tumor necrosis factor\u2010alpha and interleukin\u20101 in limb ischemia\/reperfusion injury and associated lung injury","volume":"143","author":"Seekamp A","year":"1993","journal-title":"Am J Pathol"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(19990827)82:5<765::AID-IJC23>3.0.CO;2-F"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2006.12.010"},{"key":"e_1_2_7_53_1","first-page":"1270","article-title":"Antiplatelet therapy for secondary prevention of cerebral infarction","volume":"72","author":"Tanahashi N","year":"2014","journal-title":"Nihon Rinsho"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.98.7.678"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-015-0364-3"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.3390\/md14070121"}],"container-title":["Journal of Diabetes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2F1753-0407.12667","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1753-0407.12667","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,16]],"date-time":"2023-09-16T02:30:18Z","timestamp":1694831418000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/1753-0407.12667"}},"subtitle":["\u4f4e\u5206\u5b50\u91cf\u8910\u85fb\u591a\u7cd6\u786b\u9178\u916f\u901a\u8fc7\u4fc3\u8fdb\u5185\u76ae\u578b\u4e00\u6c27\u5316\u6c2e\u5408\u6210\u9176\u78f7\u9178\u5316\u51cf\u8f7b2\u578b\u7cd6\u5c3f\u75c5\u5c0f\u9f20\u4e0b\u80a2\u7f3a\u8840\u6027\u635f\u4f24"],"short-title":[],"issued":{"date-parts":[[2018,5,17]]},"references-count":55,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2018,11]]}},"alternative-id":["10.1111\/1753-0407.12667"],"URL":"https:\/\/doi.org\/10.1111\/1753-0407.12667","archive":["Portico"],"relation":{},"ISSN":["1753-0393","1753-0407"],"issn-type":[{"value":"1753-0393","type":"print"},{"value":"1753-0407","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,5,17]]},"assertion":[{"value":"2017-06-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-03-27","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-05-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}