{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:47:28Z","timestamp":1791398848109,"version":"4.3.3"},"reference-count":27,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2001,2,2]]},"abstract":"<jats:p>\n            <jats:italic>Abstract<\/jats:italic>\n            \u2014In a previous study, we found that the p22\n            <jats:sup>\n              <jats:italic>phox<\/jats:italic>\n            <\/jats:sup>\n            subunit of the NADH\/NADPH oxidase is overexpressed in vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats (SHRs) with enhanced vascular production of superoxide anion (\n            <jats:sup>\u00b7<\/jats:sup>\n            O\n            <jats:sub>2<\/jats:sub>\n            <jats:sup>\u2212<\/jats:sup>\n            ). Thus, we have investigated whether changes in the sequence or activity of the promoter region of p22\n            <jats:sup>\n              <jats:italic>phox<\/jats:italic>\n            <\/jats:sup>\n            gene are present in SHRs. To carry out this analysis, first of all, we characterized the rat gene structure and promoter region for the p22\n            <jats:sup>\n              <jats:italic>phox<\/jats:italic>\n            <\/jats:sup>\n            subunit. The p22\n            <jats:sup>\n              <jats:italic>phox<\/jats:italic>\n            <\/jats:sup>\n            gene spans \u224810 kb and contains 6 exons and 5 introns. Primer extension analysis indicated the transcriptional start site 100 bp upstream from the translational start site. The immediate promoter region of the p22\n            <jats:sup>\n              <jats:italic>phox<\/jats:italic>\n            <\/jats:sup>\n            gene does not contain a TATA box, but there are a CCAC box and putative recognition sites for nuclear factors, such as SP1, \u03b3-interferon, and nuclear factor-\u03baB. Using reporter-gene transfection analysis, we found that this promoter was functional in VSMCs. Furthermore, we observed that p22\n            <jats:sup>\n              <jats:italic>phox<\/jats:italic>\n            <\/jats:sup>\n            promoter activity was significantly higher in VSMCs from SHRs than from normotensive Wistar-Kyoto rats. In addition, we found that there were 5 polymorphisms in the sequence of p22\n            <jats:sup>\n              <jats:italic>phox<\/jats:italic>\n            <\/jats:sup>\n            promoter between Wistar-Kyoto rats and SHRs and that they were functional. The results obtained in this study provide a tool to explore the mechanisms that regulate the expression of p22\n            <jats:sup>\n              <jats:italic>phox<\/jats:italic>\n            <\/jats:sup>\n            gene in rat VSMCs. Furthermore, our findings show that changes in the sequence of p22\n            <jats:sup>\n              <jats:italic>phox<\/jats:italic>\n            <\/jats:sup>\n            gene promoter and in the degree of activation of VSMCs are responsible for upregulated expression of p22\n            <jats:sup>\n              <jats:italic>phox<\/jats:italic>\n            <\/jats:sup>\n            in SHRs.\n          <\/jats:p>","DOI":"10.1161\/01.res.88.2.217","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:52:16Z","timestamp":1339462336000},"page":"217-222","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":44,"title":["Polymorphisms and Promoter Overactivity of the p22\n            <sup>\n              <i>phox<\/i>\n            <\/sup>\n            Gene in Vascular Smooth Muscle Cells From Spontaneously Hypertensive Rats"],"prefix":"10.1161","volume":"88","author":[{"given":"Guillermo","family":"Zalba","sequence":"first","affiliation":[{"name":"From the Vascular Pathophysiology Unit, School of Medicine, University of Navarra, Pamplona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gorka San","family":"Jose\u0301","sequence":"additional","affiliation":[{"name":"From the Vascular Pathophysiology Unit, School of Medicine, University of Navarra, Pamplona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco J.","family":"Beaumont","sequence":"additional","affiliation":[{"name":"From the Vascular Pathophysiology Unit, School of Medicine, University of Navarra, Pamplona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari\u0301a A.","family":"Fortun\u0303o","sequence":"additional","affiliation":[{"name":"From the Vascular Pathophysiology Unit, School of Medicine, University of Navarra, Pamplona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Fortun\u0303o","sequence":"additional","affiliation":[{"name":"From the Vascular Pathophysiology Unit, School of Medicine, University of Navarra, Pamplona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Di\u0301ez","sequence":"additional","affiliation":[{"name":"From the Vascular Pathophysiology Unit, School of Medicine, University of Navarra, Pamplona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_1_1_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.30.4.934"},{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.25.5.1083"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199007053230105"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.99.15.2027"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116491"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1994.266.6.H2568"},{"key":"e_1_3_1_7_2","first-page":"H2274","volume":"268","year":"1995","unstructured":"Pagano P, Ito Y, Tornheim K, Gallop P, Tauber A, Cohen R. An NADPH oxidase superoxide-generating system in the rabbit aorta. Am J Physiol. 1995;268:H2274\u2013H2280.","journal-title":"Am J Physiol"},{"key":"e_1_3_1_8_2","first-page":"H1626","volume":"271","year":"1996","unstructured":"Jones SA, O\u2019Donnell VB, Wood JD, Broughton JP, Hugher EJ, Jones OT. Expression of phagocyte NADPH oxidase components in human endothelial cells. Am J Physiol. 1996;271:H1626\u2013H1634.","journal-title":"Am J Physiol"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118623"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.86.5.494"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.38.23317"},{"key":"e_1_3_1_12_2","doi-asserted-by":"crossref","unstructured":"Zalba G Beaumont FJ San Jos\u00e9 G Fortu\u00f1o A Fortu\u00f1o MA Etayo JC D\u00edez J. Vascular NADH\/NADPH oxidase is involved in enhanced superoxide production in spontaneously hypertensive rats. Hypertension.2000;35:1055\u20131061.","DOI":"10.1161\/01.HYP.35.5.1055"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.34.1.138"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114898"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.100.14.1494"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.80.1.45"},{"key":"e_1_3_1_17_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3290653"},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.19.5.446"},{"key":"e_1_3_1_19_2","doi-asserted-by":"crossref","unstructured":"Bendhack LM Sharma RV Bhalla RC. Altered signal transduction in vascular smooth muscle cells of spontaneously hypertensive rats. 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