{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T15:21:50Z","timestamp":1789399310933,"version":"build-2803163510"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2012,8,6]]},"abstract":"\n \n Background<\/jats:italic>\n <\/jats:title>\n \n The expression of calcium\/calmodulin\u2010dependent kinase IV (\n CaMKIV<\/jats:styled-content>\n ) was hitherto thought to be confined to the nervous system. However, a recent genome\u2010wide analysis indicated an association between hypertension and a single\u2010nucleotide polymorphism (\n rs10491334<\/jats:ext-link>\n ) of the human\n CaMKIV<\/jats:styled-content>\n gene (\n \n CaMK4<\/jats:styled-content>\n <\/jats:styled-content>\n )<\/jats:italic>\n , which suggests a role for this kinase in the regulation of vascular tone.\n <\/jats:p>\n <\/jats:sec>\n \n \n Methods and Results<\/jats:italic>\n <\/jats:title>\n \n To directly assess the role of\n CaMKIV<\/jats:styled-content>\n in hypertension, we characterized the cardiovascular phenotype of\n \n CaMK4<\/jats:styled-content>\n <\/jats:styled-content>\n \u2212\/\u2212<\/jats:sup>\n mice. They displayed a typical hypertensive phenotype, including high blood pressure levels, cardiac hypertrophy, vascular and kidney damage, and reduced tolerance to chronic ischemia and myocardial infarction compared with wild\u2010type littermates. Interestingly, in vitro experiments showed the ability of this kinase to activate endothelial nitric oxide synthase. Eventually, in a population study, we found that the\n rs10491334<\/jats:ext-link>\n variant associates with a reduction in the expression levels of\n CaMKIV<\/jats:styled-content>\n in lymphocytes from hypertensive patients.\n <\/jats:p>\n <\/jats:sec>\n \n \n Conclusions<\/jats:italic>\n <\/jats:title>\n \n Taken together, our results provide evidence that\n CaMKIV<\/jats:styled-content>\n plays a pivotal role in blood pressure regulation through the control of endothelial nitric oxide synthase activity.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.112.001081","type":"journal-article","created":{"date-parts":[[2012,9,21]],"date-time":"2012-09-21T17:49:16Z","timestamp":1348249756000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":143,"title":["CaMK4 Gene Deletion Induces Hypertension"],"prefix":"10.1161","volume":"1","author":[{"given":"Gaetano","family":"Santulli","sequence":"first","affiliation":[{"name":"Department of Clinical Medicine, Cardiovascular and Immunologic Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ersilia","family":"Cipolletta","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Cardiovascular and Immunologic Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Sorriento","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Cardiovascular and Immunologic Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmine","family":"Del Giudice","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Cardiovascular and Immunologic Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Anastasio","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Cardiovascular and Immunologic 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Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annibale","family":"Puca","sequence":"additional","affiliation":[{"name":"Multimedica Research Hospital ,\rMilan, Italy"},{"name":"Department of Medicine and Surgery, University of Salerno, Salerno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Trimarco","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Cardiovascular and Immunologic Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maddalena","family":"Illario","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Biology and Pathology, \u201cFederico II\u201d University of Naples, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Iaccarino","sequence":"additional","affiliation":[{"name":"Multimedica Research Hospital ,\rMilan, Italy"},{"name":"Department of Medicine and Surgery, University of 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