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<jats:title>Methods<\/jats:title>\n                    <jats:p>Production of elastase, release of extracellular traps, adhesion, and migration were assessed in neutrophils from patients with pulmonary arterial hypertension and control subjects. Proteomic analyses were applied to explain functional perturbations, and transcriptomic data were used to find underlying mechanisms. CD66b-specific neutrophil EVs were isolated from plasma of patients with pulmonary arterial hypertension, and we determined whether they produce pulmonary hypertension in mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>Neutrophils from patients with pulmonary arterial hypertension produce and release increased neutrophil elastase, associated with enhanced extracellular traps. They exhibit reduced migration and increased adhesion attributed to elevated \u03b21-integrin and vinculin identified by proteomic analysis and previously linked to an antiviral response. This was substantiated by a transcriptomic IFN signature that we related to an increase in human endogenous retrovirus K envelope protein. Transfection of human endogenous retrovirus K envelope in a neutrophil cell line (HL-60) increases neutrophil elastase and IFN genes, whereas vinculin is increased by human endogenous retrovirus K deoxyuridine triphosphate diphosphatase that is elevated in patient plasma. Neutrophil EVs from patient plasma contain increased neutrophil elastase and human endogenous retrovirus K envelope and induce pulmonary hypertension in mice, mitigated by elafin, an elastase inhibitor.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Elevated human endogenous retroviral elements and elastase link a neutrophil innate immune response to pulmonary arterial hypertension.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.202102-0446oc","type":"journal-article","created":{"date-parts":[[2022,6,13]],"date-time":"2022-06-13T13:00:20Z","timestamp":1655125220000},"page":"1019-1034","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":37,"title":["Endogenous Retroviral Elements Generate Pathologic Neutrophils in Pulmonary Arterial 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Roger","family":"Thompson","sequence":"additional","affiliation":[{"name":"Vera Moulton Wall Center for Pulmonary Vascular Diseases"},{"name":"Stanford Cardiovascular Institute"},{"name":"Department of Pediatrics \u2013 Cardiology"},{"name":"Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria E.","family":"Ariza","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology and Genetics and"},{"name":"Institute for Behavioral Medicine Research, The Ohio State University Wexner Medical Center, Columbus, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Utkan","family":"Demirci","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roham T.","family":"Zamanian","sequence":"additional","affiliation":[{"name":"Vera Moulton Wall Center for Pulmonary Vascular Diseases"},{"name":"Department of Medicine \u2013 Pulmonary and Critical Care Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francois","family":"Haddad","sequence":"additional","affiliation":[{"name":"Stanford Cardiovascular Institute"},{"name":"Department of Medicine \u2013 Cardiovascular Medicine, Stanford University, Stanford, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark R.","family":"Nicolls","sequence":"additional","affiliation":[{"name":"Vera Moulton Wall Center for Pulmonary Vascular Diseases"},{"name":"Stanford Cardiovascular Institute"},{"name":"Department of Medicine \u2013 Pulmonary and Critical Care Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"Snyder","sequence":"additional","affiliation":[{"name":"Stanford Cardiovascular Institute"},{"name":"Department of Genetics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7886-7104","authenticated-orcid":false,"given":"Marlene","family":"Rabinovitch","sequence":"additional","affiliation":[{"name":"Vera Moulton Wall Center for Pulmonary Vascular Diseases"},{"name":"Stanford Cardiovascular Institute"},{"name":"Department of Pediatrics \u2013 Cardiology"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,10,15]]},"reference":[{"key":"2026022021161020900_bib1","doi-asserted-by":"crossref","first-page":"4306","DOI":"10.1172\/JCI60658","article-title":"Molecular pathogenesis of pulmonary arterial hypertension","volume":"122","author":"Rabinovitch","year":"2012","journal-title":"J Clin Invest"},{"key":"2026022021161020900_bib2","first-page":"632","article-title":"Pulmonary artery endothelial abnormalities in patients with congenital heart defects and pulmonary hypertension. 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