{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:05:58Z","timestamp":1789016758025,"version":"build-2803163510"},"reference-count":19,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2004,10,5]],"date-time":"2004-10-05T00:00:00Z","timestamp":1096934400000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2004,10]]},"abstract":"<jats:p>Hypoxia\u2010inducible factor (HIF) modulates transcriptional control of several genes involved in vascular growth and cellular metabolism. HIF activity can be enhanced by suppression of prolyl and asparaginyl hydroxylase activity by dimethyloxalylglycine (DMOG). We have compared the effects of DMOG treatment and femoral artery ligation individually or in combination on HIF\u20101\u03b1 protein level, HIF\u2010dependent gene expression and capillary\u2010to\u2010fibre ratio (C: F) in extensor digitorum longus and tibialis anterior muscles of mice. Immunohistochemical examination revealed that HIF\u20101\u03b1 is present in non\u2010ischaemic mouse skeletal muscles, but its amount increased profoundly in response to the combination of DMOG treatment and ischaemia. Combined treatment resulted in 39% increase in C: F in ischaemic muscles (<jats:italic>P<\/jats:italic> &lt; 0.0001 <jats:italic>versus<\/jats:italic> controls) whereas individual treatments produced little effect under our conditions. Combined treatment led to a significant increase in endogenous HIF\u20101\u03b1 protein (6.14 \u00b1 1.1 <jats:italic>versus<\/jats:italic> 1.17 \u00b1 0.2 in controls; <jats:italic>P<\/jats:italic> &lt; 0.05) that was not apparent in mice treated with DMOG or femoral artery ligation alone. Ischaemia increased vascular endothelial growth factor (VEGF) protein production by 2.5\u2010fold (<jats:italic>P<\/jats:italic> &lt; 0.05 <jats:italic>versus<\/jats:italic> controls), irrespective of DMOG treatment. However, production of the VEGF receptor Flk\u20101 was more enhanced in ischaemic + DMOG\u2010treated muscles (<jats:italic>P<\/jats:italic> &lt; 0.001 and <jats:italic>P<\/jats:italic> &lt; 0.05 compared with controls and untreated ischaemic muscles, respectively), which may explain the intensive growth of capillaries in those muscles. The findings indicate that treatment with DMOG has a potential therapeutic use in promoting angiogenesis in ischaemic diseases, and perhaps for improving muscle recovery after injury, exercise or training.<\/jats:p>","DOI":"10.1113\/jphysiol.2004.069757","type":"journal-article","created":{"date-parts":[[2004,8,20]],"date-time":"2004-08-20T02:54:50Z","timestamp":1092970490000},"page":"21-26","source":"Crossref","is-referenced-by-count":123,"title":["Inhibition of endogenous HIF inactivation induces angiogenesis in ischaemic skeletal muscles of mice"],"prefix":"10.1113","volume":"560","author":[{"given":"Malgorzata","family":"Milkiewicz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher W.","family":"Pugh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart","family":"Egginton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2004,10,5]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-132-11-200006060-00005"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1069825"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0603-653"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2003.10.002"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M211298200"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1059796"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/hh0202.104923"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/71527"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20030035"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-894X(03)00539-0"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-894X(03)00149-5"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-200105000-00002"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(02)00259-6"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.01-0125com"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1201047"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.102.18.2255"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.02-1062fje"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.162119399"},{"key":"e_1_2_5_20_1","first-page":"66","article-title":"Angiogenic response to mechanical stimuli in mouse skeletal muscle","volume":"49","author":"Williams J","year":"2002","journal-title":"J Vasc Res"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1113%2Fjphysiol.2004.069757","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/jphysiol.2004.069757","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T13:03:15Z","timestamp":1696942995000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/jphysiol.2004.069757"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,10]]},"references-count":19,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2004,10]]}},"alternative-id":["10.1113\/jphysiol.2004.069757"],"URL":"https:\/\/doi.org\/10.1113\/jphysiol.2004.069757","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,10]]}}}