{"doi":"10.1016/j.jacbts.2022.02.021","title":"Reduced Proteolytic Cleavage of von Willebrand Factor Leads to Aortic Valve Stenosis and Load-Dependent Ventricular Remodeling","abstract":"We hypothesized that excess endothelial-associated von Willebrand factor (vWF) and secondary platelet adhesion contribute to aortic valve stenosis (AS). We studied hyperlipidemic mice lacking ADAMTS13 (LDLR−/−AD13−/−), which cleaves endothelial-associated vWF multimers. On echocardiography and molecular imaging, LDLR−/−AD13−/− compared with control strains had increased aortic endothelial vWF and platelet adhesion and developed hemodynamically significant AS, arterial stiffening, high valvulo-aortic impedance, and secondary load-dependent reduction in LV systolic function. Histology revealed leaflet thickening and calcification with valve interstitial cell myofibroblastic and osteogenic transformation, and evidence for TGFβ1 pathway activation. We conclude that valve leaflet endothelial vWF-platelet interactions promote AS through juxtacrine platelet signaling.","journal":"JACC Basic to Translational Science","year":2022,"id":282523,"datarank":0.31191623125197543,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"self_citation_contribution":0.31191623125197543,"citation_network_contribution":0.0,"self_endowment_contribution":0.31191623125197543,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9619,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":341549,"name":"Matthew Muller","orcid":"0000-0002-5079-1889","position":1,"is_corresponding":false},{"id":341550,"name":"Oleg Varlamov","orcid":"0000-0003-0294-215X","position":2,"is_corresponding":false},{"id":385954,"name":"Matthew Hagen","orcid":"0000-0002-9812-2262","position":3,"is_corresponding":false},{"id":343139,"name":"William Packwood","orcid":null,"position":4,"is_corresponding":false},{"id":305760,"name":"Terry K. Morgan","orcid":"0000-0003-0742-5012","position":5,"is_corresponding":false},{"id":341553,"name":"Aris Xie","orcid":"0009-0001-0888-9989","position":6,"is_corresponding":false},{"id":310089,"name":"Clàudia López","orcid":null,"position":7,"is_corresponding":false},{"id":299570,"name":"Dominic W. Chung","orcid":"0000-0002-2645-5703","position":8,"is_corresponding":false},{"id":299569,"name":"Junmei Chen","orcid":"0000-0001-6702-2763","position":9,"is_corresponding":false},{"id":356754,"name":"José A. López","orcid":"0000-0002-2550-5131","position":10,"is_corresponding":false},{"id":341555,"name":"Jonathan R. Lindner","orcid":"0000-0003-2604-5277","position":11,"is_corresponding":false},{"id":341548,"name":"Koya Ozawa","orcid":"0000-0002-8401-3727","position":0,"is_corresponding":true}],"reference_count":37,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:29:19.691592Z","pmid":"35958695","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":[]}