ArticleProceedings of the National Academy of Sciences of the United States of America2023
Sulfated oligosaccharide activates endothelial Notch for inducing macrophage-associated arteriogenesis to treat ischemic diseases.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 15 citations in OpenAlex.
- Posttranslational modifications in regulating Notch signaling pathway and tumor angiogenesis: from molecular mechanisms to therapeutic applications.Journal of molecular cell biology · 2026Review
- Sulfated polysaccharide reprograms arterialized angiogenesis of endochondral ossification to rescue defective osteonecrosis therapy.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- An "inside-out"-guided genetically engineered hydrogel for augmenting aged bone regeneration.Bioactive materials · 2025Article
- Dual-Modular Hydrogel Microparticles with Precision-Modulation of Inflammatory Microenvironment Dictate Full-Thickness Cartilage Regeneration for Osteoarthritis Repair.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Selumetinib promotes coronary collateral circulation by inducing M2-like macrophage polarization following myocardial infarction.Acta pharmacologica Sinica · 2025Article
- GelMA@LNP/AST Promotes eNOS-Dependent Angiogenesis Through Autophagy Activation for the Treatment of Hind Limb Ischemia.International journal of nanomedicine · 2025Article
- Comparison of the protective effects of chitosan oligosaccharides and chitin oligosaccharide on apoptosis, inflammation and oxidative stress.Experimental and therapeutic medicine · 2024Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
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' (Mφs') differentiation into perivascular Mφs, 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 Mφs 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.
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Registered trials
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