{"doi":"10.1161/atvbaha.111.229609","title":"Essential Domains of A Disintegrin and Metalloprotease With Thrombospondin Type 1 Repeats-13 Metalloprotease Required for Modulation of Arterial Thrombosis","abstract":"<jats:sec>\n            <jats:title>Objective—</jats:title>\n            <jats:p>A disintegrin and metalloprotease with thrombospondin type 1 repeats-13 (ADAMTS13) inhibits platelet aggregation and arterial thrombosis by cleavage of von Willebrand factor. However, the structural components of ADAMTS13 required for inhibition of arterial thrombosis are not fully defined.</jats:p>\n          </jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results—</jats:title>\n            <jats:p>\n              Using recombinant proteins and a murine model, we demonstrated that an ADAMTS13 variant truncated after either the eighth thrombospondin type 1 repeat or the spacer domain inhibits ferric chloride–induced arterial thrombosis in\n              <jats:italic>ADAMTS13</jats:italic>\n              <jats:sup>−/−</jats:sup>\n              mice with efficacy similar to that of full-length ADAMTS13. The results obtained from monitoring thrombus formation in carotid and mesenteric arteries were highly concordant. Further analyses by site-directed mutagenesis and human monoclonal antibody inhibition assay revealed that the Cys-rich and spacer domains of ADAMTS13, particularly the amino acid residues between Arg559 and Glu664 in the spacer domain, may be critical for modulation of arterial thrombosis in vivo. Finally, the thrombosis-modulating function of ADAMTS13 and variants/mutants was highly correlated with the von Willebrand factor–cleavage activity under fluid shear stress.\n            </jats:p>\n          </jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion—</jats:title>\n            <jats:p>Our results suggest that the amino terminus of ADAMTS13, specifically the variable region of the spacer domain, is crucial for modulation of arterial thromboses under (patho)physiological conditions. These findings shed more light on the structure-function relationship of ADAMTS13 in vivo and may be applicable for rational design of protein- or gene-based therapy of arterial thromboses.</jats:p>\n          </jats:sec>","journal":"Arteriosclerosis, Thrombosis, and Vascular Biology","year":2011,"id":20349,"datarank":1.2362719463512764,"base_score":3.912023005428146,"endowment":3.912023005428146,"self_citation_contribution":0.586803450814222,"citation_network_contribution":0.6494684955370542,"self_endowment_contribution":0.586803450814222,"citer_contribution":0.6494684955370542,"corpus_percentile":null,"corpus_rank":null,"citation_count":49,"citer_count":20,"citers_with_citation_signal":16,"citers_with_endowment":16,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":134818,"name":"Sheng-Yu Jin","orcid":null,"position":1,"is_corresponding":false},{"id":134819,"name":"Jing Xue","orcid":null,"position":2,"is_corresponding":false},{"id":134820,"name":"Nicoletta Sorvillo","orcid":null,"position":3,"is_corresponding":false},{"id":134821,"name":"Jan Voorberg","orcid":null,"position":4,"is_corresponding":false},{"id":134823,"name":"X. Long Zheng","orcid":null,"position":5,"is_corresponding":false},{"id":134817,"name":"Juan Xiao","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":3.912023005428146,"endowment":3.912023005428146,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"21799176","pmcid":null,"openalex_id":"https://openalex.org/W2170321681","authors":[],"funders":[{"funder_name":"NHLBI NIH HHS","grant_id":"P01 HL074124","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"R01 HL079027","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"HL-079027","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"HL-074124","title":null}],"total_grants":4,"fwci":1.1213,"citation_percentile":0.7744891,"influential_citations":0,"citation_trend":[{"year":2012,"count":4},{"year":2013,"count":4},{"year":2014,"count":1},{"year":2015,"count":7},{"year":2016,"count":5},{"year":2017,"count":3},{"year":2018,"count":1},{"year":2019,"count":3},{"year":2020,"count":1},{"year":2021,"count":1},{"year":2022,"count":4},{"year":2023,"count":3},{"year":2024,"count":5},{"year":2025,"count":4},{"year":2026,"count":3}],"oa_status":"bronze","license":null,"oa_locations":[{"url":"https://www.ahajournals.org/doi/pdf/10.1161/ATVBAHA.111.229609","host_type":"journal"},{"url":"https://www.ahajournals.org/doi/pdf/10.1161/ATVBAHA.111.229609","host_type":"BRONZE"},{"url":"https://www.ahajournals.org/doi/pdf/10.1161/ATVBAHA.111.229609","host_type":"publisher"},{"url":"https://www.ahajournals.org/doi/full/10.1161/ATVBAHA.111.229609","host_type":"publisher"},{"url":"https://doi.org/10.1161/atvbaha.111.229609","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/21799176","host_type":"repository"},{"url":"https://pure.amsterdamumc.nl/en/publications/dbc37764-ab67-4a29-bc75-8c2b10b96601","host_type":"repository"},{"url":"https://pure.amc.nl/en/publications/essential-domains-of-a-disintegrin-and-metalloprotease-with-thrombospondin-type-1-repeats13-metalloprotease-required-for-modulation-of-arterial-thrombosis(4bdbf70d-c3b7-4c30-b26a-5b636533e4b2).html","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3174348","host_type":"repository"}],"fields_of_study":["Complement system in diseases","Platelet Disorders and Treatments","Cell Adhesion Molecules Research","Chemistry","Medicine","Biology","ADAM Proteins","ADAMTS13 Protein","Animals","Antibodies, Monoclonal","Carotid Stenosis","Chlorides","Disease Models, Animal","Dogs","Ferric Compounds","HEK293 Cells","Half-Life","Humans","Kinetics","Mesenteric Vascular Occlusion","Metalloendopeptidases","Mice","Mice, Knockout","Mutagenesis, Site-Directed","Mutation","Protein Structure, Tertiary","Recombinant Proteins","Structure-Activity Relationship","Thrombosis","Transfection","von Willebrand Factor"],"mesh_terms":["ADAMTS13 Protein","Animals","Antibodies, Monoclonal","Chlorides","Disease Models, Animal","Dogs","Ferric Compounds","Half-Life","Humans","Kinetics","Mesenteric Vascular Occlusion","Metalloendopeptidases","Mutation","Recombinant Proteins","Structure-Activity Relationship","Thrombosis","Transfection","von Willebrand Factor","Mutagenesis, Site-Directed","Carotid Stenosis","Protein Structure, Tertiary","Mice, Knockout","Mice","ADAM Proteins","HEK293 Cells"],"keywords":["Thrombospondin","Disintegrin","Metalloproteinase","Matrix metalloproteinase","Biology","Genetics"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-04T08:57:40.604273Z","pmid":null,"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":[]}