{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:53:36Z","timestamp":1787018016303,"version":"build-2736575974"},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2014,1]]},"abstract":"<jats:sec>\n                    <jats:title>Objective\u2014<\/jats:title>\n                    <jats:p>\n                      Involvement of reactive oxygen species derived from nicotinamide adenine dinucleotide phosphate, reduced form (NADPH) oxidase has been documented in the development of hypoxia-induced model of pulmonary arterial hypertension (PAH). Because the PAH-like phenotype was demonstrated in mice deficient in\n                      <jats:italic>Nox1<\/jats:italic>\n                      gene (Nox1\n                      <jats:sup>\u2212\/Y<\/jats:sup>\n                      ) raised under normoxia, the aim of this study was to clarify how the lack of NOX1\/NADPH oxidase could lead to pulmonary pathology.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Approach and Results\u2014<\/jats:title>\n                    <jats:p>\n                      Spontaneous enlargement and hypertrophy of the right ventricle, accompanied by hypertrophy of pulmonary vessels, were demonstrated in Nox1\n                      <jats:sup>\u2212\/Y<\/jats:sup>\n                      9 to 18 weeks old. Because an increased number of \u03b1-smooth muscle actin-positive vessels were observed in Nox1\n                      <jats:sup>\u2212\/Y<\/jats:sup>\n                      , pulmonary arterial smooth muscle cells (PASMCs) were isolated and characterized by flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. In Nox1\n                      <jats:sup>\u2212\/Y<\/jats:sup>\n                      PASMCs, the number of apoptotic cells was significantly reduced without any change in the expression of endothelin-1, and hypoxia-inducible factors HIF-1\u03b1 and HIF-2\u03b1, factors implicated in the pathogenesis of PAH. A significant decrease in a voltage-dependent K\n                      <jats:sup>+<\/jats:sup>\n                      channel, Kv1.5 protein, and an increase in intracellular potassium levels were demonstrated in Nox1\n                      <jats:sup>\u2212\/Y<\/jats:sup>\n                      PASMCs. When a rescue study was performed in Nox1\n                      <jats:sup>\u2212\/Y<\/jats:sup>\n                      crossed with transgenic mice overexpressing rat\n                      <jats:italic>Nox1<\/jats:italic>\n                      gene, impaired apoptosis and the level of Kv1.5 protein in PASMCs were almost completely recovered in Nox1\n                      <jats:sup>\u2212\/Y<\/jats:sup>\n                      harboring the\n                      <jats:italic>Nox1<\/jats:italic>\n                      transgene.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\u2014<\/jats:title>\n                    <jats:p>These findings suggest a critical role for NOX1 in cellular apoptosis by regulating Kv1.5 and intracellular potassium levels. Because dysfunction of Kv1.5 is among the features demonstrated in PAH, inactivation of NOX1\/NADPH oxidase may be a causative factor for pulmonary vascular remodeling associated with PAH.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/atvbaha.113.302107","type":"journal-article","created":{"date-parts":[[2013,11,15]],"date-time":"2013-11-15T00:58:19Z","timestamp":1384477099000},"page":"110-119","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":34,"title":["Deficiency of NOX1\/Nicotinamide Adenine Dinucleotide Phosphate, Reduced Form Oxidase Leads to Pulmonary Vascular Remodeling"],"prefix":"10.1161","volume":"34","author":[{"given":"Kazumi","family":"Iwata","sequence":"first","affiliation":[{"name":"From the Departments of Pharmacology (K. Iwata, K. Ikami, K.M., M.I., M.M., W.C., J.Z., K.Z., C.Y.-N.), Anatomy and Developmental Biology (D.S., T. Yokoyama), and Radioisotope Center (M.K.), Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Regenerative Medicine and Stem Cell Biology, University of Tsukuba, Tsukuba, Japan (T. Yamashita, O.O.); Department of Biomedical Engineering, Sapporo Medical University School of Medicine, Sapporo, Japan (N.T., Y.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanako","family":"Ikami","sequence":"additional","affiliation":[{"name":"From the Departments of Pharmacology (K. Iwata, K. Ikami, K.M., M.I., M.M., W.C., J.Z., K.Z., C.Y.-N.), Anatomy and Developmental Biology (D.S., T. Yokoyama), and Radioisotope Center (M.K.), Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Regenerative Medicine and Stem Cell Biology, University of Tsukuba, Tsukuba, Japan (T. Yamashita, O.O.); Department of Biomedical Engineering, Sapporo Medical University School of Medicine, Sapporo, Japan (N.T., Y.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuniharu","family":"Matsuno","sequence":"additional","affiliation":[{"name":"From the Departments of Pharmacology (K. Iwata, K. Ikami, K.M., M.I., M.M., W.C., J.Z., K.Z., C.Y.-N.), Anatomy and Developmental Biology (D.S., T. Yokoyama), and Radioisotope Center (M.K.), Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Regenerative Medicine and Stem Cell Biology, University of Tsukuba, Tsukuba, Japan (T. Yamashita, O.O.); Department of Biomedical Engineering, Sapporo Medical University School of Medicine, Sapporo, Japan (N.T., Y.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiharu","family":"Yamashita","sequence":"additional","affiliation":[{"name":"From the Departments of Pharmacology (K. Iwata, K. Ikami, K.M., M.I., M.M., W.C., J.Z., K.Z., C.Y.-N.), Anatomy and Developmental Biology (D.S., T. Yokoyama), and Radioisotope Center (M.K.), Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Regenerative Medicine and Stem Cell Biology, University of Tsukuba, Tsukuba, Japan (T. Yamashita, O.O.); Department of Biomedical Engineering, Sapporo Medical University School of Medicine, Sapporo, Japan (N.T., Y.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dai","family":"Shiba","sequence":"additional","affiliation":[{"name":"From the Departments of Pharmacology (K. Iwata, K. Ikami, K.M., M.I., M.M., W.C., J.Z., K.Z., C.Y.-N.), Anatomy and Developmental Biology (D.S., T. Yokoyama), and Radioisotope Center (M.K.), Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Regenerative Medicine and Stem Cell Biology, University of Tsukuba, Tsukuba, Japan (T. Yamashita, O.O.); Department of Biomedical Engineering, Sapporo Medical University School of Medicine, Sapporo, Japan (N.T., Y.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masakazu","family":"Ibi","sequence":"additional","affiliation":[{"name":"From the Departments of Pharmacology (K. Iwata, K. Ikami, K.M., M.I., M.M., W.C., J.Z., K.Z., C.Y.-N.), Anatomy and Developmental Biology (D.S., T. Yokoyama), and Radioisotope Center (M.K.), Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Regenerative Medicine and Stem Cell Biology, University of Tsukuba, Tsukuba, Japan (T. Yamashita, O.O.); Department of Biomedical Engineering, Sapporo Medical University School of Medicine, Sapporo, Japan (N.T., Y.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Misaki","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"From the Departments of Pharmacology (K. Iwata, K. Ikami, K.M., M.I., M.M., W.C., J.Z., K.Z., C.Y.-N.), Anatomy and Developmental Biology (D.S., T. Yokoyama), and Radioisotope Center (M.K.), Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Regenerative Medicine and Stem Cell Biology, University of Tsukuba, Tsukuba, Japan (T. Yamashita, O.O.); Department of Biomedical Engineering, Sapporo Medical University School of Medicine, Sapporo, Japan (N.T., Y.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masato","family":"Katsuyama","sequence":"additional","affiliation":[{"name":"From the Departments of Pharmacology (K. Iwata, K. Ikami, K.M., M.I., M.M., W.C., J.Z., K.Z., C.Y.-N.), Anatomy and Developmental Biology (D.S., T. Yokoyama), and Radioisotope Center (M.K.), Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Regenerative Medicine and Stem Cell Biology, University of Tsukuba, Tsukuba, Japan (T. 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