CaMK4 gene deletion induces hypertension

Gaetano Santulli, Ersilia Cipolletta, Daniela Sorriento, Carmine Del Giudice, Antonio Anastasio, Sara Monaco, Angela Serena Maione, Gianluigi Condorelli, Annibale Puca, Bruno Trimarco, Maddalena Illario, Guido Iaccarino

Research output: Contribution to journalArticle

127 Scopus citations

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.

Original languageEnglish (US)
Article numbere001081
JournalJournal of the American Heart Association
Volume1
Issue number4
DOIs
StatePublished - Aug 2012

Keywords

  • Angiogenesis
  • Arrhythmia
  • Endothelium
  • Hypertension
  • Hypertrophy

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Santulli, G., Cipolletta, E., Sorriento, D., Del Giudice, C., Anastasio, A., Monaco, S., Maione, A. S., Condorelli, G., Puca, A., Trimarco, B., Illario, M., & Iaccarino, G. (2012). CaMK4 gene deletion induces hypertension. Journal of the American Heart Association, 1(4), [e001081]. https://doi.org/10.1161/JAHA.112.001081