{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T16:53:55Z","timestamp":1762102435955,"version":"build-2065373602"},"reference-count":70,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,10,30]],"date-time":"2019-10-30T00:00:00Z","timestamp":1572393600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C33043\/A24478","CRUK C8218\/A18673"],"award-info":[{"award-number":["C33043\/A24478","CRUK C8218\/A18673"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["FS\/14\/66\/31293","RG\/16\/7\/32357"],"award-info":[{"award-number":["FS\/14\/66\/31293","RG\/16\/7\/32357"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Coronary microvascular dysfunction combined with maladaptive cardiomyocyte morphology and energetics is a major contributor to heart failure advancement. Thus, dually enhancing cardiac angiogenesis and targeting cardiomyocyte function to slow, or reverse, the development of heart failure is a logical step towards improved therapy. We present evidence for the potential to repurpose a former anti\u2010cancer Arg\u2010Gly\u2010Asp (RGD)\u2010mimetic pentapeptide, cilengitide, here used at low doses. Cilengitide targets \u03b1v\u03b23 integrin and this protein is upregulated in human dilated and ischaemic cardiomyopathies. Treatment of mice after abdominal aortic constriction (AAC) surgery with low\u2010dose cilengitide (ldCil) enhances coronary angiogenesis and directly affects cardiomyocyte hypertrophy with an associated reduction in disease severity. At a molecular level, ldCil treatment has a direct effect on cardiac endothelial cell transcriptomic profiles, with a significant enhancement of pro\u2010angiogenic signalling pathways, corroborating the enhanced angiogenic phenotype after ldCil treatment. Moreover, ldCil treatment of Angiotensin II\u2010stimulated AngII\u2010stimulated cardiomyocytes significantly restores transcriptomic profiles similar to those found in normal human heart. The significance of this finding is enhanced by transcriptional similarities between AngII\u2010treated cardiomyocytes and failing human hearts. Taken together, our data provide evidence supporting a possible new strategy for improved heart failure treatment using low\u2010dose RGD\u2010mimetics with relevance to human disease. \u00a9 2019 The Authors.\n                    <jats:italic>The Journal of Pathology<\/jats:italic>\n                    published by John Wiley &amp; Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.5340","type":"journal-article","created":{"date-parts":[[2019,8,19]],"date-time":"2019-08-19T11:18:12Z","timestamp":1566213492000},"page":"523-535","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Repurposing an anti\u2010cancer agent for the treatment of hypertrophic heart disease"],"prefix":"10.1002","volume":"249","author":[{"given":"Matthew","family":"Dukinfield","sequence":"first","affiliation":[{"name":"Barts Cancer Institute, Queen Mary University of London, John Vane Science Centre, Charterhouse Square  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleni","family":"Maniati","sequence":"additional","affiliation":[{"name":"Barts Cancer Institute, Queen Mary University of London, John Vane Science Centre, Charterhouse Square  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6075-1808","authenticated-orcid":false,"given":"Louise E","family":"Reynolds","sequence":"additional","affiliation":[{"name":"Barts Cancer Institute, Queen Mary University of London, John Vane Science Centre, Charterhouse Square  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aisah","family":"Aubdool","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute, Queen Mary University of London, Charterhouse Square  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reshma S","family":"Baliga","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute, Queen Mary University of London, Charterhouse Square  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriela","family":"D'Amico","sequence":"additional","affiliation":[{"name":"Barts Cancer Institute, Queen Mary University of London, John Vane Science Centre, Charterhouse Square  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oscar","family":"Maiques","sequence":"additional","affiliation":[{"name":"Barts Cancer Institute, Queen Mary University of London, John Vane Science Centre, Charterhouse Square  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Wang","sequence":"additional","affiliation":[{"name":"Barts Cancer Institute, Queen Mary University of London, John Vane Science Centre, Charterhouse Square  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr","given":"Kenneth C","family":"Bedi","sequence":"additional","affiliation":[{"name":"Perelman School of Medicine University of Pennsylvania, Translational Research Center  Philadelphia PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth B","family":"Margulies","sequence":"additional","affiliation":[{"name":"Perelman School of Medicine University of Pennsylvania, Translational Research Center  Philadelphia PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victoria","family":"Sanz\u2010Moreno","sequence":"additional","affiliation":[{"name":"Barts Cancer Institute, Queen Mary University of London, John Vane Science Centre, Charterhouse Square  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adrian","family":"Hobbs","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute, Queen Mary University of London, Charterhouse Square  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kairbaan","family":"Hodivala\u2010Dilke","sequence":"additional","affiliation":[{"name":"Barts Cancer Institute, Queen Mary University of London, John Vane Science Centre, Charterhouse Square  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,10,30]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.310039"},{"key":"e_1_2_7_3_1","first-page":"1365","article-title":"Angiogenic gene therapy in cardiovascular diseases: dream or vision?","volume":"38","author":"Yla\u2010Herttuala S","year":"2017","journal-title":"Eur Heart J"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.98.25.2800"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1095-1085"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.athoracsur.2003.09.060"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3302416"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.110.220855"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvq267"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2012.145"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(93)90790-8"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(00)00988-8"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00971-6"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2015.10"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2011.03.014"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.08-127480"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-016-0598-6"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200420352"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.111.091652"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-017-1245-1"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1136\/heartjnl-2016-310115"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvn033"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6600141"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7512751"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1023\/B:AGEN.0000011801.98187.f2"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-05-023580"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.06.6514"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1941"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2014.10.015"},{"key":"e_1_2_7_30_1","first-page":"503","article-title":"Primary mouse endothelial cell culture for assays of angiogenesis","volume":"120","author":"Reynolds LE","year":"2006","journal-title":"Methods Mol Med"},{"key":"e_1_2_7_31_1","first-page":"1729","article-title":"Transverse aortic constriction in mice","volume":"38","author":"AC dA","year":"2010","journal-title":"J Vis Exp"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0089559"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcha.2016.03.007"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.112.000438"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2012.04835.x"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00405.2011"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M302028200"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvs140"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-015-9473-6"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-13-0446"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kft161"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10534-010-9382-5"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-03-2408"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.060037197"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep35930"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.21902"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.82.11.1145"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2009.05100.x"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33718"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1161\/hy02t2.102796"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.113.002186"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2017.03.001"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.113.300376"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.2174\/138161211796390976"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygeno.2014.12.002"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000051363.86009.3C"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm970832g"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.2174\/187152010794728639"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1002\/ange.19971091304"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1093\/bmb\/ldw025"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00049.2017"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.13-245753"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.112.248674"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature17040"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.101825"},{"key":"e_1_2_7_66_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0522-3"},{"key":"e_1_2_7_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13541"},{"key":"e_1_2_7_68_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3317"},{"key":"e_1_2_7_69_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu638"},{"key":"e_1_2_7_70_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv007"},{"key":"e_1_2_7_71_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506580102"}],"container-title":["The Journal of Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.5340","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/path.5340","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.5340","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T16:45:46Z","timestamp":1761065146000},"score":1,"resource":{"primary":{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/10.1002\/path.5340"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,30]]},"references-count":70,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["10.1002\/path.5340"],"URL":"https:\/\/doi.org\/10.1002\/path.5340","archive":["Portico"],"relation":{},"ISSN":["0022-3417","1096-9896"],"issn-type":[{"type":"print","value":"0022-3417"},{"type":"electronic","value":"1096-9896"}],"subject":[],"published":{"date-parts":[[2019,10,30]]},"assertion":[{"value":"2019-03-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-08-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-10-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}