PURPOSE: Protein kinase plays an essential role in controlling cardiac growth 
and hypertrophic remodeling. The cardiac troponin I-interacting kinase (TNNI3K), 
a novel cardiac specific kinase, is associated with cardiomyocyte hypertrophy. 
However, the precise function of TNNI3K in regulating cardiac remodeling has 
remained controversial.
METHODS AND RESULTS: In a rat model of cardiac hypertrophy generated by 
transverse aortic constriction, myocardial TNNI3K expression was significantly 
increased by 1.62 folds (P<0.05) after constriction for 15 days. To investigate 
the role of TNNI3K in cardiac hypertrophy, we generated transgenic mouse lines 
with overexpression of human TNNI3K specifically in the heart. At the age of 3 
months, the high-copy-number TNNI3K transgenic mice demonstrated a phenotype of 
concentric hypertrophy with increased heart weight normalized to body weight 
(1.31 fold, P<0.01). Echocardiography and non-invasive hemodynamic assessments 
showed enhanced cardiac function. No necrosis or myocyte disarray was observed 
in the heart of TNNI3K transgenic mice. This concentric hypertrophy maintained 
up to 12 months of age without cardiac dysfunction. The phospho amino acid 
analysis revealed that TNNI3K is a protein-tyrosine kinase. The yeast two-hybrid 
screen and co-immunoprecipitation assay identified cTnI as a target for TNNI3K. 
Moreover, TNNI3K overexpression induced cTnI phosphorylation at Ser22/Ser23 in 
vivo and in vitro, suggesting that TNNI3K is a novel upstream regulator for cTnI 
phosphorylation.
CONCLUSION: TNNI3K promotes a concentric hypertrophy with enhancement of cardiac 
function via regulating the phosphorylation of cTnI. TNNI3K could be a potential 
therapeutic target for preventing from heart failure.