CaMK4 Gene Deletion Induces Hypertension.

Authors:
Gaetano Santulli
Gaetano Santulli
Federico II University of Naples
Italy
Ersilia Cipolletta
Ersilia Cipolletta
Department of Clinical Medicine
Italy
Daniela Sorriento
Daniela Sorriento
Department of Clinical Medicine
Italy
Antonio Anastasio
Antonio Anastasio
Department of Clinical Medicine
Italy
Sara Monaco
Sara Monaco
University of Pittsburgh Medical Center
United States
Angela Serena Maione
Angela Serena Maione
University of Naples Federico II
Italy
Gianluigi Condorelli
Gianluigi Condorelli
Humanitas Clinical and Research Center
Rozzano | Italy

J Am Heart Assoc 2012 Aug 24;1(4):e001081. Epub 2012 Aug 24.

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.).

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.

Methods And 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.).

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http://dx.doi.org/10.1161/JAHA.112.001081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3487344PMC
August 2012
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References

(Supplied by CrossRef)
Purification and characterization of a brainā€specific multifunctional calmodulinā€dependent protein kinase from rat cerebellum
Miyano O et al.
J Biol Chem 1992

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