文献类型：期刊文献

英文题名：Sulfated oligosaccharide activates endothelial Notch for inducing macrophage- associated arteriogenesis to treat ischemic diseases

作者：Yu, Yuanman[1,2];Wang, Shuang[3];Chen, Xinye[2];Gao, Zehua[3];Dai, Kai[1];Wang, Jing[1,2];Liu, Changsheng[2,3]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Frontiers Sci Ctr Materiobiol & Dynam Chem, Shanghai 200237, Peoples R China;[3]East China Univ Sci & Technol, Key Lab Ultrafine Mat, Minist Educ, Shanghai 200237, Peoples R China

年份：2023

卷号：120

期号：46

外文期刊名：PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001146686100009)】；

基金：This research was supported by the Basic Science Center Program of National Natural Science Foundation of China (No. T2288102) , the Key Program of the National Natural Science Foundation of China (No. 32230059) , the National Natural Science Foundation of China (No. 32101086) , the National Postdoctoral Program for Innovative Talents (BX2021101) , and the China Postdoctoral Science Foundation Funded Project (2021M701192) , Fundamental Research Funds for the Central Universities (JKD01221507) , and the Foundation of Frontiers Science Center for Materiobiology and Dynamic Chemistry (JKVD1211002) . This study was also supported by the 111 Project (B14018) .

语种：英文

外文关键词：ischemic diseases; in situ regeneration; therapeutic arteriogenesis; sulfated oligosaccharide; perivascular macrophage

摘要：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 sponta-neous generation of collateral circulation and blood reperfusion in rodent models of hind limb ischemia and myocardial infarction. SCOS elicits anti- inflammatory macrophages' (M phi s') differentiation into perivascular M phi s, 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 phi s 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 har-nessed to direct efficiently therapeutic arteriogenesis and perfusion for the treatment of ischemic diseases.