Format

Send to:

Choose Destination
See comment in PubMed Commons below
J Am Heart Assoc. 2012 Aug;1(4):e001081. doi: 10.1161/JAHA.112.001081. Epub 2012 Aug 24.

CaMK4 Gene Deletion Induces Hypertension.

Author information

  • 1Department 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.).

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.

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.).

KEYWORDS:

angiogenesis; arrhythmia; endothelium; hypertension; hypertrophy

PMID:
23130158
[PubMed]
PMCID:
PMC3487344
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk