{"doi":"10.7554/elife.67777","title":"Endothelial pannexin 1–TRPV4 channel signaling lowers pulmonary arterial pressure in mice","abstract":"Pannexin 1 (Panx1), an ATP-efflux pathway, has been linked with inflammation in pulmonary capillaries. However, the physiological roles of endothelial Panx1 in the pulmonary vasculature are unknown. Endothelial transient receptor potential vanilloid 4 (TRPV4) channels lower pulmonary artery (PA) contractility and exogenous ATP activates endothelial TRPV4 channels. We hypothesized that endothelial Panx1-ATP-TRPV4 channel signaling promotes vasodilation and lowers pulmonary arterial pressure (PAP). Endothelial, but not smooth muscle, knockout of Panx1 increased PA contractility and raised PAP in mice. Flow/shear stress increased ATP efflux through endothelial Panx1 in PAs. Panx1-effluxed extracellular ATP signaled through purinergic P2Y2 receptor (P2Y2R) to activate protein kinase Cα (PKCα), which in turn activated endothelial TRPV4 channels. Finally, caveolin-1 provided a signaling scaffold for endothelial Panx1, P2Y2R, PKCα, and TRPV4 channels in PAs, promoting their spatial proximity and enabling signaling interactions. These results indicate that endothelial Panx1-P2Y2R-TRPV4 channel signaling, facilitated by caveolin-1, reduces PA contractility and lowers PAP in mice.","journal":"eLife","year":2021,"id":158648,"datarank":0.5742962094733643,"base_score":3.828641396489095,"endowment":3.828641396489095,"self_citation_contribution":0.5742962094733643,"citation_network_contribution":0.0,"self_endowment_contribution":0.5742962094733643,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":45,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9522,"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":346363,"name":"Matteo Ottolini","orcid":null,"position":1,"is_corresponding":false},{"id":308460,"name":"Yen‐Lin Chen","orcid":"0000-0003-1149-394X","position":2,"is_corresponding":false},{"id":668679,"name":"Eliska Klimentova","orcid":null,"position":3,"is_corresponding":false},{"id":667982,"name":"Maniselvan Kuppusamy","orcid":"0000-0003-4579-584X","position":4,"is_corresponding":false},{"id":667983,"name":"Soham A. Shah","orcid":"0000-0002-7622-0603","position":5,"is_corresponding":false},{"id":461401,"name":"Richard D. Minshall","orcid":"0000-0003-3164-475X","position":6,"is_corresponding":false},{"id":668680,"name":"Cheikh I. Seye","orcid":null,"position":7,"is_corresponding":false},{"id":518939,"name":"Victor E. Laubach","orcid":"0000-0001-9673-5383","position":8,"is_corresponding":false},{"id":190934,"name":"Brant E. Isakson","orcid":"0000-0002-7692-6294","position":9,"is_corresponding":false},{"id":308461,"name":"Swapnil K. Sonkusare","orcid":"0000-0001-9587-9342","position":10,"is_corresponding":false},{"id":344553,"name":"Zdravka Daneva","orcid":"0000-0002-1141-9697","position":0,"is_corresponding":true}],"reference_count":62,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:44:30.791367Z","pmid":"34490843","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":[]}