{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T02:36:56Z","timestamp":1792291016847,"version":"4.4.0"},"reference-count":54,"publisher":"National Academy of Sciences","issue":"46","license":[{"start":{"date-parts":[[2023,11,9]],"date-time":"2023-11-09T00:00:00Z","timestamp":1699488000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["T2288102"],"award-info":[{"award-number":["T2288102"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32230059"],"award-info":[{"award-number":["32230059"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32101086"],"award-info":[{"award-number":["32101086"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012152","name":"China Postdoctoral Foundation Project | National Postdoctoral Program for Innovative Talents","doi-asserted-by":"publisher","award":["BX2021101"],"award-info":[{"award-number":["BX2021101"]}],"id":[{"id":"10.13039\/501100012152","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,11,14]]},"abstract":"<jats:p>Ischemic diseases lead to considerable morbidity and mortality, yet conventional clinical treatment strategies for therapeutic angiogenesis fall short of being impactful. Despite the potential of biomaterials to deliver pro-angiogenic molecules at the infarct site to induce angiogenesis, their efficacy has been impeded by aberrant vascular activation and off-target circulation. Here, we present a semisynthetic low-molecular sulfated chitosan oligosaccharide (SCOS) that efficiently induces therapeutic arteriogenesis with a spontaneous generation of collateral circulation and blood reperfusion in rodent models of hind limb ischemia and myocardial infarction. SCOS elicits anti-inflammatory macrophages\u2019 (M\u03c6s\u2019) differentiation into perivascular M\u03c6s, which in turn directs artery formation via a cell-to-cell communication rather than secretory factor regulation. SCOS-mediated arteriogenesis requires a canonical Notch signaling pathway in M\u03c6s via the glycosylation of protein O-glucosyltransferases 2, which results in promoting arterial differentiation and tissue repair in ischemia. Thus, this highly bioactive oligosaccharide can be harnessed to direct efficiently therapeutic arteriogenesis and perfusion for the treatment of ischemic diseases.<\/jats:p>","DOI":"10.1073\/pnas.2307480120","type":"journal-article","created":{"date-parts":[[2023,11,9]],"date-time":"2023-11-09T13:39:49Z","timestamp":1699537189000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":22,"title":["Sulfated oligosaccharide activates endothelial Notch for inducing macrophage-associated arteriogenesis to treat ischemic diseases"],"prefix":"10.1073","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0030-7881","authenticated-orcid":false,"given":"Yuanman","family":"Yu","sequence":"first","affiliation":[{"name":"The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, People\u2019s Republic of China"},{"name":"Frontiers Science Center for Materiobiology and Dynamic Chemistry, East China University of Science and Technology, Shanghai 200237, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinye","family":"Chen","sequence":"additional","affiliation":[{"name":"Frontiers Science Center for Materiobiology and Dynamic Chemistry, East China University of Science and Technology, Shanghai 200237, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zehua","family":"Gao","sequence":"additional","affiliation":[{"name":"Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6551-8463","authenticated-orcid":false,"given":"Kai","family":"Dai","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, People\u2019s Republic of China"},{"name":"Frontiers Science Center for Materiobiology and Dynamic Chemistry, East China University of Science and Technology, Shanghai 200237, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changsheng","family":"Liu","sequence":"additional","affiliation":[{"name":"Frontiers Science Center for Materiobiology and Dynamic Chemistry, East China University of Science and Technology, Shanghai 200237, People\u2019s Republic of China"},{"name":"Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2023,11,9]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000001052"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nnano.2017.167"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aaz8011"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-24804-3"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abl3888"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3003841"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2021.09.013"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/gt.2011.93"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-14480-0"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202101873"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10507"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.08.039"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aay6391"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-00953-2"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.6b00654"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abq6900"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2018.02.031"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2019.10.018"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M207057200"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202010732"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abd8217"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2019.01.192"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.carbpol.2021.118699"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.carbpol.2020.116271"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2019.104323"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00041.2008"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10237-016-0811-4"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-016-0007"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0809784106"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.12.010"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12384-2"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.304718"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.04.007"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-018-0056-9"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3555"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-021-09793-7"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1261093"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M806202200"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-03314-y"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2019.03.503"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abm3436"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2018.11.018"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2018.09.010"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2014.10.017"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2021.03.038"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.120.318380"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000143013.04985.E7"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0206087"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.2174\/157016113804547629"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01323"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.108.179705"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04596-2"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.13.9604"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-020-00294-x"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2307480120","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,9]],"date-time":"2023-11-09T13:39:54Z","timestamp":1699537194000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2307480120"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,9]]},"references-count":54,"journal-issue":{"issue":"46","published-print":{"date-parts":[[2023,11,14]]}},"alternative-id":["10.1073\/pnas.2307480120"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2307480120","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,9]]},"assertion":[{"value":"2023-05-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-01","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2307480120"}}