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Knockout of cardiac troponin I‐interacting kinase leads to cardiac dysfunction and remodelling

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Cardiac troponin I‐interacting kinase (TNNI3K) is a cardiac‐specific kinase that has been identified as a diagnostic marker and a therapeutic target in cardiovascular diseases. However, the biological function of TNNI3K… Click to show full abstract

Cardiac troponin I‐interacting kinase (TNNI3K) is a cardiac‐specific kinase that has been identified as a diagnostic marker and a therapeutic target in cardiovascular diseases. However, the biological function of TNNI3K in cardiac dysfunction and remodelling remains elusive. In the present study, a Tnni3k cardiomyocyte‐specific knockout (Tnni3k‐cKO) mouse model was established. Echocardiography was used to evaluate cardiac function in mice. Heart failure markers were detected using enzyme‐linked immunosorbent assay. Haematoxylin and eosin staining, wheat germ agglutinin staining, Masson's trichrome staining, Sirius red staining and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining were used to assess histopathological changes, cardiac hypertrophy, collagen deposition and myocardial apoptosis, respectively. Expression levels of TNNI3K, apoptosis‐related proteins, and p38 mitogen‐activated protein kinase were measured using Western blot analysis. Compared to wild‐type controls, cardiac dysfunction and cardiac remodelling of Tnni3k‐cKO mice increased gradually with age. Tnni3k‐cKO mice exhibited cardiac hypertrophy, cardiac fibrosis and cardiomyocyte apoptosis. Upregulation of cleaved caspase‐3 in Tnni3k‐cKO mice appeared to be related to phosphorylation and activation of the p38 mitogen‐activated protein kinase signalling pathway. In conclusion, this study shows that TNNI3K is essential for cardiac development and function, providing new insights into the development of novel therapeutic strategies for cardiac diseases.

Keywords: tnni3k; kinase; troponin interacting; cardiac dysfunction; cardiac troponin

Journal Title: Clinical and Experimental Pharmacology and Physiology
Year Published: 2022

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