{"doi":"10.1016/j.jbc.2021.101315","title":"Intracellular receptor EPAC regulates von Willebrand factor secretion from endothelial cells in a PI3K-/eNOS-dependent manner during inflammation","abstract":"Coagulopathy is associated with both inflammation and infection, including infections with novel severe acute respiratory syndrome coronavirus-2, the causative agent Coagulopathy is associated with both inflammation and infection, including infection with novel severe acute respiratory syndrome coronavirus-2, the causative agent of COVID-19. Clot formation is promoted via cAMP-mediated secretion of von Willebrand factor (vWF), which fine-tunes the process of hemostasis. The exchange protein directly activated by cAMP (EPAC) is a ubiquitously expressed intracellular cAMP receptor that plays a regulatory role in suppressing inflammation. To assess whether EPAC could regulate vWF release during inflammation, we utilized our EPAC1-null mouse model and revealed increased secretion of vWF in endotoxemic mice in the absence of the EPAC1 gene. Pharmacological inhibition of EPAC1 in vitro mimicked the EPAC1-/- phenotype. In addition, EPAC1 regulated tumor necrosis factor-α-triggered vWF secretion from human umbilical vein endothelial cells in a manner dependent upon inflammatory effector molecules PI3K and endothelial nitric oxide synthase. Furthermore, EPAC1 activation reduced inflammation-triggered vWF release, both in vivo and in vitro. Our data delineate a novel regulatory role for EPAC1 in vWF secretion and shed light on the potential development of new strategies to control thrombosis during inflammation.","journal":"Journal of Biological Chemistry","year":2021,"id":200524,"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":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9586,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":453507,"name":"Ben Zhang","orcid":"0000-0002-1176-2604","position":1,"is_corresponding":false},{"id":454227,"name":"Zhengchen Su","orcid":null,"position":2,"is_corresponding":false},{"id":453505,"name":"Yakun Liu","orcid":"0000-0002-7778-2309","position":3,"is_corresponding":false},{"id":453508,"name":"Thomas R. Shelite","orcid":"0000-0001-6686-6032","position":4,"is_corresponding":false},{"id":562043,"name":"Qing Chang","orcid":"0000-0002-7923-7814","position":5,"is_corresponding":false},{"id":642659,"name":"Yuan Qiu","orcid":"0000-0002-9572-9106","position":6,"is_corresponding":false},{"id":454228,"name":"Jiani Bei","orcid":null,"position":7,"is_corresponding":false},{"id":383917,"name":"Pingyuan Wang","orcid":"0009-0005-0368-5070","position":8,"is_corresponding":false},{"id":235604,"name":"Alexander Bukreyev","orcid":"0000-0002-0342-4824","position":9,"is_corresponding":false},{"id":426957,"name":"Lynn Soong","orcid":"0000-0003-3370-3434","position":10,"is_corresponding":false},{"id":284814,"name":"Yang Jin","orcid":"0000-0002-4779-531X","position":11,"is_corresponding":false},{"id":229178,"name":"Thomas G. Ksiazek","orcid":null,"position":12,"is_corresponding":false},{"id":563206,"name":"Angelo Gaitas","orcid":"0000-0003-4428-3949","position":13,"is_corresponding":false},{"id":254588,"name":"Shannan L. Rossi","orcid":"0000-0003-2450-2374","position":14,"is_corresponding":false},{"id":107272,"name":"Jia Zhou","orcid":"0000-0002-2811-1090","position":15,"is_corresponding":false},{"id":563207,"name":"Michael Laposata","orcid":"0000-0001-5562-3174","position":16,"is_corresponding":false},{"id":453514,"name":"Taís B. Saito","orcid":"0000-0002-0337-4441","position":17,"is_corresponding":false},{"id":453515,"name":"Bin Gong","orcid":"0000-0002-3929-3897","position":18,"is_corresponding":false},{"id":453506,"name":"Jie Xiao","orcid":"0000-0002-4718-1174","position":0,"is_corresponding":true}],"reference_count":120,"raw_metadata":null,"created_at":"2026-07-18T23:50:48.624274Z","pmid":"34678311","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":[]}