{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T10:34:04Z","timestamp":1791196444528,"version":"4.1.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2014,9,1]],"date-time":"2014-09-01T00:00:00Z","timestamp":1409529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>NF-\u03baB and IL-6, a NF-\u03baB downstream mediator, play a central role in the inflammatory response of tissues. We aimed to determine the role of the classical NF-\u03baB pathway in severe pulmonary arterial hypertension (PAH) induced by SU5416 and chronic hypoxia (SuHx) in rats. Tissue samples from patients with idiopathic PAH (iPAH) and control subjects were investigated. SuHx rats were treated from Days 1 to 3, 1 to 21, and 29 to 42 with the NF-\u03baB inhibitor pyrrolidine dithiocarbamate (PDTC) and\/or from Days 1 to 21 with anti\u2013IL-6 antibody. Nuclear staining for NF-\u03baB, an indicator of the activation of the classical NF-\u03baB pathway, was detected in pulmonary arterial lesions of patients with iPAH and SuHx rats. NF-\u03baB inhibition with PDTC prevented and reduced pulmonary arterial obliteration without reducing muscularization. However, the elevated lung levels of IL-6 were not reduced in PDTC-treated SuHx animals. PDTC treatment prevented or reduced apoptosis of pulmonary artery wall cells and pulmonary arterial obliteration. IL-6 inhibition had only a partial effect on apoptosis and obliteration. Pulmonary arterial media wall thickness was not affected by any of these treatments. Preventive and therapeutic PDTC treatment promoted immune regulation by increasing the number of perivascular CD4+ T cells, in particular regulatory T cells (early treatment), and by reducing the number of perivascular CD8+ T lymphocytes and CD45RA+ B lymphocytes. Therapeutic PDTC treatment further preserved right ventricular function in SuHx animals. Inhibition of NF-\u03baB may represent a therapeutic option for pulmonary arterial obliteration via reduced vessel wall cell apoptosis and improved regulation of the immune system.<\/jats:p>","DOI":"10.1165\/rcmb.2013-0355oc","type":"journal-article","created":{"date-parts":[[2014,3,31]],"date-time":"2014-03-31T14:53:56Z","timestamp":1396277636000},"page":"413-425","source":"Crossref","is-referenced-by-count":78,"title":["Nuclear Factor \u03baB Inhibition Reduces Lung Vascular Lumen Obliteration in Severe Pulmonary Hypertension in Rats"],"prefix":"10.1093","volume":"51","author":[{"given":"Daniela","family":"Farkas","sequence":"first","affiliation":[{"name":"Victoria Johnson Center for Lung Research, Department of Internal Medicine, Division of Pulmonary Disease and Critical Care, Virginia Commonwealth University, Richmond, Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aysar A.","family":"Alhussaini","sequence":"additional","affiliation":[{"name":"Victoria Johnson Center for Lung Research, Department of Internal Medicine, Division of Pulmonary Disease and Critical Care, Virginia Commonwealth University, Richmond, Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donatas","family":"Kraskauskas","sequence":"additional","affiliation":[{"name":"Victoria Johnson Center for Lung Research, Department of Internal Medicine, Division of Pulmonary Disease and Critical Care, Virginia Commonwealth University, Richmond, Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vita","family":"Kraskauskiene","sequence":"additional","affiliation":[{"name":"Victoria Johnson Center for Lung Research, Department of Internal Medicine, Division of Pulmonary Disease and Critical Care, Virginia Commonwealth University, Richmond, Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlyne D.","family":"Cool","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Colorado at Denver, Denver, Colorado; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark R.","family":"Nicolls","sequence":"additional","affiliation":[{"name":"Department of Medicine, Stanford University School of Medicine, Stanford, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramesh","family":"Natarajan","sequence":"additional","affiliation":[{"name":"Victoria Johnson Center for Lung Research, Department of Internal Medicine, Division of Pulmonary Disease and Critical Care, Virginia Commonwealth University, Richmond, Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laszlo","family":"Farkas","sequence":"additional","affiliation":[{"name":"Victoria Johnson Center for Lung Research, Department of Internal Medicine, Division of Pulmonary Disease and Critical Care, Virginia Commonwealth University, Richmond, 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