{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T14:37:02Z","timestamp":1776523022320,"version":"3.51.2"},"reference-count":63,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,8,10]],"date-time":"2023-08-10T00:00:00Z","timestamp":1691625600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001030","name":"National Heart Foundation of Australia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001030","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003550","name":"Queensland Government","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003550","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100016058","name":"Townsville Hospital and Health Service","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100016058","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Metabolism Res"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Diabetes is a key risk factor for ischaemic foot disease, which causes pain, tissue loss, hospital admission, and major amputation. Currently, treatment focuses on revascularisation, but many patients are unsuitable for surgery and revascularisation is frequently unsuccessful. The authors describe recent research in animal models and clinical trials investigating novel medical targets for ischaemia, including theories about impaired wound healing, animal models for limb ischaemia and recent randomised controlled trials testing novel medical therapies. Novel targets identified in animal models included stimulating mobilisation of CD34+ progenitor cells through upregulating oncostatin <jats:italic>M<\/jats:italic> or microRNA\u2010181, downregulating tumour necrosis factor superfamily member 14, or activating the Wingless pathway. Within the ischaemic limb vasculature, upregulation of apolipoprotein <jats:italic>L<\/jats:italic> domain containing 1, microRNA\u2010130b or long noncoding RNA that enhances endothelial nitric oxide synthase expression promoted limb blood supply recovery, angiogenesis, and arteriogenesis. Similarly, administration of soluble guanylate cyclase stimulators riociguat or praliciguat or 3\u2010ketoacyl\u2010CoA thiolase inhibitor trimetazidine promoted blood flow recovery. Translating pre\u2010clinical findings to patients has been challenging, mainly due to limitations in clinically translatable animal models of human disease. Promising results have been reported for administering plasmids encoding hepatocyte growth factor or intra\u2010arterial injection of bone marrow derived cells in small clinical trials. It remains to be seen whether these high resource therapies can be developed to be widely applicable. In conclusion, an ever\u2010expanding list of potential targets for medical revascularisation is being identified. It is hoped that through ongoing research and further larger clinical trials, these will translate into new broadly applicable therapies to improve outcomes.<\/jats:p>","DOI":"10.1002\/dmrr.3703","type":"journal-article","created":{"date-parts":[[2023,8,11]],"date-time":"2023-08-11T02:39:23Z","timestamp":1691721563000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Recent developments in targets for ischemic foot disease"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5779-8848","authenticated-orcid":false,"given":"Jonathan","family":"Golledge","sequence":"first","affiliation":[{"name":"Queensland Research Centre for Peripheral Vascular Disease College of Medicine and Dentistry James Cook University  Townsville Queensland Australia"},{"name":"The Department of Vascular and Endovascular Surgery The Townsville University Hospital  Townsville Queensland Australia"},{"name":"The Australian Institute of Tropical Health and Medicine James Cook University  Townsville Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0322-6147","authenticated-orcid":false,"given":"Shivshankar","family":"Thanigaimani","sequence":"additional","affiliation":[{"name":"Queensland Research Centre for Peripheral Vascular Disease College of Medicine and Dentistry James Cook University  Townsville Queensland Australia"},{"name":"The Australian Institute of Tropical Health and Medicine James Cook University  Townsville Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristen S.","family":"Barratt","sequence":"additional","affiliation":[{"name":"Queensland Research Centre for Peripheral Vascular Disease College of Medicine and Dentistry James Cook University  Townsville Queensland Australia"},{"name":"The Australian Institute of Tropical Health and Medicine James Cook University  Townsville Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6510-2097","authenticated-orcid":false,"given":"Gian Paolo","family":"Fadini","sequence":"additional","affiliation":[{"name":"University Hospital of Padova  Padova Italy"},{"name":"Veneto Institute of Molecular Medicine  Padua Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,8,10]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2019.02.016"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.3657"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41569\u2010021\u201000663\u20109"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjdrc\u20102020\u2010001676"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1042\/cs20150435"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010020\u201060352\u20104"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2008.06.011"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00270\u2010010\u20100024\u20107"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mvr.2019.103912"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/scrt245"},{"issue":"8","key":"e_1_2_12_12_1","first-page":"1167","article-title":"[Comparison of three approaches to establishing Balb\/c mouse models of hind\u2010limb ischemia]","volume":"34","author":"Chen Y","year":"2014","journal-title":"Nan Fang Yi Ke Da Xue Xue Bao"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2008.07.063"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci44490"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0272\u20106386(86)80132\u20109"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1918163117"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202216671"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125\u2010013\u20102918\u20109"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11152430"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2014.10.106"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2023.01.001"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2014\u20102751"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2021.22607"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010021\u201004294\u20103"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3887"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2023.04.007"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.2337\/db15\u20100863"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1089\/wound.2019.0943"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.78046"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1161\/atvbaha.116.307634"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102015\u201003\u2010631572"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125\u2010020\u201005142\u20103"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24086997"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.add2632"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.2337\/db14\u20101473"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13577\u2010023\u201000874\u2010x"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.163041"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.163360"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10456\u2010023\u201009870\u2010z"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010\u2010023\u201004666\u20107"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/cbdd.14248"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.2040-4603.2019.tb00084.x"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1161\/jaha.122.026586"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2023.03.017"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.122.322033"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci161759"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1080\/07853890.2021.1925147"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2208541120"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2020.290"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2019.10.017"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvir.2020.09.003"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.semvascsurg.2017.12.001"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1159\/000527309"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1177\/1526602820919951"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/sctm.20\u20100033"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.1253\/circj.cj\u201017\u20100720"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2017.11.088"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1253\/circj.cj\u201017\u20100045"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejvs.2023.03.028"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apmr.2021.02.027"},{"issue":"1","key":"e_1_2_12_61_1","first-page":"21","article-title":"Rivaroxaban and aspirin in patients with symptomatic lower extremity peripheral artery disease: a subanalysis of the COMPASS randomized clinical trial","volume":"6","author":"Kaplovitch E","year":"2021","journal-title":"JAMA Cardiol"},{"key":"e_1_2_12_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2022.08.007"},{"key":"e_1_2_12_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2022.08.001"},{"key":"e_1_2_12_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2017.09.026"}],"container-title":["Diabetes\/Metabolism Research and Reviews"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/dmrr.3703","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T04:39:40Z","timestamp":1758083980000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/dmrr.3703"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,10]]},"references-count":63,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,3]]}},"alternative-id":["10.1002\/dmrr.3703"],"URL":"https:\/\/doi.org\/10.1002\/dmrr.3703","archive":["Portico"],"relation":{},"ISSN":["1520-7552","1520-7560"],"issn-type":[{"value":"1520-7552","type":"print"},{"value":"1520-7560","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,10]]},"assertion":[{"value":"2023-07-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-08-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e3703"}}