{"doi":"10.1002/bit.27580","title":"New soluble angiopoietin analog of Hepta‐ANG1 prevents pathological vascular leakage","abstract":"Vascular leak is a key driver of organ injury in diseases, and strategies that reduce enhanced permeability and vascular inflammation are promising therapeutic targets. Activation of the angiopoietin-1 (ANG1)-Tie2 tyrosine kinase signaling pathway is an important regulator of vascular quiescence. Here we describe the design and construction of a new soluble ANG1 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 ANG1 with a heptameric scaffold derived from the C-terminus of serum complement protein C4-binding protein α. We refer to this new fusion protein biologic as Hepta-ANG1, which forms a stable heptamer and induces Tie2 phosphorylation in cultured cells, and in the lung following intravenous injection of mice. Injection of Hepta-ANG1 ameliorates vascular endothelial growth factor- and lipopolysaccharide-induced vascular leakage, in keeping with the known functions of Angpt1-Tie2 in maintaining quiescent vascular stability. The new Hepta-ANG1 fusion is easy to produce and displays remarkable stability with high multimericity that can potently activate Tie2. It could be a new candidate ANG1 mimetic therapy for treatments of inflammatory vascular leak, such as acute respiratory distress syndrome and sepsis.","journal":"Biotechnology and Bioengineering","year":2020,"id":72638,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9498,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":384216,"name":"Michael Ryczko","orcid":null,"position":1,"is_corresponding":false},{"id":382975,"name":"Xinfang Xie","orcid":"0000-0002-0872-2986","position":2,"is_corresponding":false},{"id":382976,"name":"Jason Baardsnes","orcid":"0000-0001-5587-3034","position":3,"is_corresponding":false},{"id":384217,"name":"Simon Lord‐Dufour","orcid":null,"position":4,"is_corresponding":false},{"id":384218,"name":"Yves Duroche","orcid":null,"position":5,"is_corresponding":false},{"id":382977,"name":"Emily Anne Hicks","orcid":"0009-0009-8208-7675","position":6,"is_corresponding":false},{"id":382978,"name":"Aftab Taiyab","orcid":"0000-0002-5546-9928","position":7,"is_corresponding":false},{"id":382979,"name":"Heather Sheardown","orcid":"0000-0002-5404-635X","position":8,"is_corresponding":false},{"id":245996,"name":"Susan E. Quaggin","orcid":"0000-0002-3706-5727","position":9,"is_corresponding":false},{"id":347811,"name":"Jing Jin","orcid":"0000-0001-7023-5305","position":10,"is_corresponding":false},{"id":382974,"name":"Pan Liu","orcid":"0000-0002-3066-652X","position":0,"is_corresponding":true}],"reference_count":42,"raw_metadata":null,"created_at":"2026-07-18T21:45:09.279825Z","pmid":"32970320","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}