TY - JOUR
T1 - CaMK4 gene deletion induces hypertension
AU - Santulli, Gaetano
AU - Cipolletta, Ersilia
AU - Sorriento, Daniela
AU - Del Giudice, Carmine
AU - Anastasio, Antonio
AU - Monaco, Sara
AU - Maione, Angela Serena
AU - Condorelli, Gianluigi
AU - Puca, Annibale
AU - Trimarco, Bruno
AU - Illario, Maddalena
AU - Iaccarino, Guido
PY - 2012/8
Y1 - 2012/8
N2 - 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.
AB - 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.
KW - Angiogenesis
KW - Arrhythmia
KW - Endothelium
KW - Hypertension
KW - Hypertrophy
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U2 - 10.1161/JAHA.112.001081
DO - 10.1161/JAHA.112.001081
M3 - Article
AN - SCOPUS:84872681370
SN - 2047-9980
VL - 1
JO - Journal of the American Heart Association
JF - Journal of the American Heart Association
IS - 4
M1 - e001081
ER -