{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T12:30:03Z","timestamp":1790685003179,"version":"4.1.0"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2018,6,19]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">NADPH Oxidase 5 (Nox5) is a calcium\u2010sensitive superoxide\u2010generating Nox. It is present in lower forms and higher mammals, but not in rodents. Nox5 is expressed in vascular cells, but the functional significance remains elusive. Given that contraction is controlled by calcium and reactive oxygen species, both associated with Nox5, we questioned the role of Nox5 in pro\u2010contractile signaling and vascular function.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Transgenic mice expressing human Nox5 in a vascular smooth muscle cell\u2013specific manner (Nox5 mice) and\n              <jats:italic>Rhodnius prolixus<\/jats:italic>\n              , an arthropod model that expresses Nox5 endogenoulsy, were studied. Reactive oxygen species generation was increased systemically and in the vasculature and heart in Nox5 mice. In Nox5\u2010expressing mice, agonist\u2010induced vasoconstriction was exaggerated and endothelium\u2010dependent vasorelaxation was impaired. Vascular structural and mechanical properties were not influenced by Nox5. Vascular contractile responses in Nox5 mice were normalized by\n              <jats:italic>N<\/jats:italic>\n              \u2010acetylcysteine and inhibitors of calcium channels, calmodulin, and endoplasmic reticulum ryanodine receptors, but not by\n              <jats:styled-content style=\"fixed-case\">GKT<\/jats:styled-content>\n              137831 (Nox1\/4 inhibitor). At the cellular level, vascular changes in Nox5 mice were associated with increased vascular smooth muscle cell [Ca\n              <jats:sup>2+<\/jats:sup>\n              ]\n              <jats:sub>i<\/jats:sub>\n              , increased reactive oxygen species and nitrotyrosine levels, and hyperphosphorylation of pro\u2010contractile signaling molecules\n              <jats:styled-content style=\"fixed-case\">MLC<\/jats:styled-content>\n              20 (myosin light chain 20) and\n              <jats:styled-content style=\"fixed-case\">MYPT<\/jats:styled-content>\n              1 (myosin phosphatase target subunit 1). Blood pressure was similar in wild\u2010type and Nox5 mice. Nox5 did not amplify angiotensin II effects. In\n              <jats:italic>R. prolixus<\/jats:italic>\n              , gastrointestinal smooth muscle contraction was blunted by Nox5 silencing, but not by\n              <jats:styled-content style=\"fixed-case\">VAS<\/jats:styled-content>\n              2870 (Nox1\/2\/4 inhibitor).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Nox5 is a pro\u2010contractile Nox isoform important in redox\u2010sensitive contraction. This involves calcium\u2010calmodulin and endoplasmic reticulum\u2013regulated mechanisms. Our findings define a novel function for vascular Nox5, linking calcium and reactive oxygen species to the pro\u2010contractile molecular machinery in vascular smooth muscle cells.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.118.009388","type":"journal-article","created":{"date-parts":[[2018,6,15]],"date-time":"2018-06-15T09:15:33Z","timestamp":1529054133000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":66,"title":["NADPH Oxidase 5 Is a Pro\u2010Contractile Nox Isoform and a Point of Cross\u2010Talk for Calcium and Redox Signaling\u2010Implications in Vascular Function"],"prefix":"10.1161","volume":"7","author":[{"given":"Augusto C.","family":"Montezano","sequence":"first","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences University of Glasgow United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Livia","family":"De Lucca Camargo","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences University of Glasgow United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrik","family":"Persson","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences University of Glasgow United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco J.","family":"Rios","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences University of Glasgow United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam P.","family":"Harvey","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences University of Glasgow United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aikaterini","family":"Anagnostopoulou","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences University of Glasgow United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Palacios","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences University of Glasgow United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Caroline P.","family":"Gandara","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Bioqu\u00edmica de Artr\u00f3podes Hemat\u00f3fagos Instituto de Bioqu\u00edmica M\u00e9dica Leopoldo De Meis Programa de Biologia Molecular e Biotecnologia Universidade Federal do Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rheure","family":"Alves\u2010Lopes","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences University of Glasgow United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karla B.","family":"Neves","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences University of Glasgow United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Dulak\u2010Lis","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences University of Glasgow United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chet E.","family":"Holterman","sequence":"additional","affiliation":[{"name":"Kidney Research Centre Ottawa Hospital Research Institute University of Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro Lagerblad","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Bioqu\u00edmica de Artr\u00f3podes Hemat\u00f3fagos Instituto de Bioqu\u00edmica M\u00e9dica Leopoldo De Meis Programa de Biologia Molecular e Biotecnologia Universidade Federal do Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delyth","family":"Graham","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences University of Glasgow United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Kennedy","sequence":"additional","affiliation":[{"name":"Kidney Research Centre Ottawa Hospital Research Institute University of Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhian M.","family":"Touyz","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences University of Glasgow United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1179\/174329210X12650506623401"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.111.243972"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/antiox6020040"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2013.5302"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2017.05.002"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.112.132159"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.116.07668"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2016.00284"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1124\/mi.11.1.5"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.112.267054"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1042\/CS20120330"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2006.10.054"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(01)00449-8"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00910.2011"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1042\/CS20100384"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1702293114"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M103034200"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M310268200"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M608966200"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.110.070193"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0100102"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1019956529549"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a006023"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2008.04.024"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.109.216036"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2008.07.063"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2013.01.278"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2013040371"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.2337\/db16-1585"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.117.001778"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12862-017-0940-0"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2010.00872.x"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.116.07699"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.101.14.1653"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-6625-7_27"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.107.103192"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000158845.49943.5e"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000054200.44505.AB"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.877191"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.114.303733"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2007.02.047"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2007.11.013"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2014-0141OC"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.084939"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi1020088"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.019729"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-7843.2011.00785.x"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2148-7-178"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2007.03.006"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.118.009388","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T11:28:41Z","timestamp":1715599721000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.118.009388"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,6,19]]},"references-count":50,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2018,6,19]]}},"alternative-id":["10.1161\/JAHA.118.009388"],"URL":"https:\/\/doi.org\/10.1161\/jaha.118.009388","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,6,19]]},"assertion":[{"value":"2018-04-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-05-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-06-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e009388"}}