title: CaMK4 Gene Deletion Induces Hypertension.
abstract: BACKGROUND
  The expression of calcium/calmodulin-dependent kinase IV (CaMKIV) was hitherto thought to be confined to the nervous system. However, a recent genome-wide analysis indicated an association between hypertension and a single-nucleotide polymorphism (rs10491334) of the human CaMKIV gene (CaMK4), which suggests a role for this kinase in the regulation of vascular tone.
  
  
  RESULTS
  To directly assess the role of CaMKIV in hypertension, we characterized the cardiovascular phenotype of CaMK4(-/-) 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-type 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 rs10491334 variant associates with a reduction in the expression levels of CaMKIV in lymphocytes from hypertensive patients.
  
  
  CONCLUSIONS
  Taken together, our results provide evidence that CaMKIV plays a pivotal role in blood pressure regulation through the control of endothelial nitric oxide synthase activity. (J Am Heart Assoc. 2012;1:e001081 doi: 10.1161/JAHA.112.001081.).
authors.affiliation: Department of Clinical Medicine, Cardiovascular and Immunologic Sciences, "Federico II" University of Naples,  Naples, Italy (G.S., E.C., D.S., C.D.G., A.A., B.T.).
authors.forename: Gaetano
authors.initials: G
authors.lastname: Santulli
authors.forename: Ersilia
authors.initials: E
authors.lastname: Cipolletta
authors.forename: Daniela
authors.initials: D
authors.lastname: Sorriento
authors.forename: Carmine
authors.initials: C
authors.lastname: Del Giudice
authors.forename: Antonio
authors.initials: A
authors.lastname: Anastasio
authors.forename: Sara
authors.initials: S
authors.lastname: Monaco
authors.forename: Angela Serena
authors.initials: AS
authors.lastname: Maione
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Condorelli
authors.forename: Annibale
authors.initials: A
authors.lastname: Puca
authors.forename: Bruno
authors.initials: B
authors.lastname: Trimarco
authors.forename: Maddalena
authors.initials: M
authors.lastname: Illario
authors.forename: Guido
authors.initials: G
authors.lastname: Iaccarino
keywords: angiogenesis; arrhythmia; endothelium; hypertension; hypertrophy