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http://conacyt.repositorioinstitucional.mx/jspui/handle/1000/2356| New Soluble Angiopoietin Analog of C4BP-ANG1 Prevents Pathological Vascular Leakage | |
| Liu Pan. Ryczko Michael. Xie Xinfang. Taiyab Aftab. Sheardown Heather. Quaggin Susan. Jin Jing. | |
| Acceso Abierto | |
| Atribución-NoComercial-SinDerivadas | |
| 10.1101/2020.03.30.016147 | |
| Vascular leak is a key driver of organ injury in diseases such as Acute Respiratory Distress Syndrome caused by viruses, including COVID-19. Strategies that reduce enhanced permeability and vascular inflammation are promising therapeutic targets. Activation of the Angiopoietin-1 (Angpt1)-Tie2 tyrosine kinase signaling pathway is an important regulator of vascular quiescence. Here we describe the design and construction of a new soluble ANGPT1 mimetic that is a potent activator of endothelial Tie2 in vitro and in vivo. Using a chimeric fusion strategy, we replaced the extracellular matrix (ECM) binding and oligomerization domain of ANGPT1 with a heptameric scaffold derived from the C-terminus of serum complement protein C4-binding protein α (C4BP). We refer to this new fusion protein biologic as C4BP-ANG1, which forms a stable heptamer and induces TIE2 phosphorylation in cultured cells, and in the lung following i.v. injection of mice. Injection of C4BP-ANG1 ameliorates VEGF- and lipopolysaccharide-induced vascular leakage, in keeping with the known functions of Angpt1-Tie2 in maintaining quiescent vascular stability, and therefore is a promising candidate treatment for inflammatory endothelial dysfunction. | |
| www.biorxiv.org | |
| 2020 | |
| Artículo | |
| https://www.biorxiv.org/content/biorxiv/early/2020/04/01/2020.03.30.016147.full.pdf | |
| Inglés | |
| VIRUS RESPIRATORIOS | |
| Aparece en las colecciones: | Artículos científicos |
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