DOI: 10.5176/2345-7201_1.2.22

Authors:  Yang Xu, Jie Tian and Xupei Huang


Troponin, a contractile protein of the thin filament of striated muscle, consists of three subunits: troponin C (TnC), troponin T (TnT), and troponin I (TnI). Cardiac troponin I (cTnI) plays a critical role in regulation of cardiac function. The physiological effect of cTnI, as an inhibitory subunit of troponin complex, is to prevent the interaction between myosin heavy chain heads and actins, i.e. the cross-bridge formation, and to ensure a proper relaxation of cardiac myofilaments. In pathological conditions, the deficiency of cTnI or mutations in cTnI especially in the C-terminus of cTnI is associated with diastolic dysfunction caused by myofibril hypersensitivity to Ca2+. Our laboratory has generated cTnI knockout mouse model to investigate the cellular and molecular function of cTnI and created cTnI mutant disease mouse models to explore the pathophysiology caused by cTnI mutations in the heart. Here, we present our recent studies on physiological function of cTnI in the heart and the pathological consequences caused by the cTnI mutations in the diseased heart using the transgenic mouse models. The mechanisms underlying diastolic dysfunction and heart failure caused by cTnI mutations are explored in cell-based assays and in transgenic animal models. These studies provide us with useful information in searching for therapeutic strategies and target-oriented medication for the treatment of diastolic dysfunction and heart failure.

Keywords: troponin— myofilament; gene mutation; cardiomyopathy; heart failure; transgenic mice

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