Biochemical markers -- Diagnostic use

Restrictive cardiomyopathy (RCM) is represented in part by left ventricular stiffness
and diastolic dysfunction. Missense mutations of the cardiac troponin I (cTnI) gene cause
idiopathic RCM. These mutations are located in the C-terminus of cTnI and affect cardiac
relaxation. Transgenic mouse models presenting the pathology observed in clinical
patients with RCM have been generated previously and express the mutant cTnI in their
hearts. RCM-linked mutations increase cardiac myofilament Ca2+ sensitivity and promote
diastolic dysfunction in the heart. Previous studies using double transgenic mice
(cTnI/R193H/ND) showed that ventricular relaxation is enhanced in the cTnI/R193H
transgenic mice. In this study, another double transgenic mouse model,
(cTnI/R193H/ND/KO), provides an avenue to investigate its rescuing effects on RCMlinked
mutations in the cTnI /R193H/KO mouse. Use of molecular biological techniques,
transgenic animal developments and murine echocardiography in this study has
culminated into a greater understanding of RCM and diastolic dysfunction.

Restrictive cardiomyopathy (RCM) is a cardiac muscle disorder characterized by increased ventricular stiffness and diastolic dysfunction. Patients with RCM often present severe cardiac problems which usually lead to heart failure and sudden death. No effective treatment is available for RCM which makes the finding of novel efficient therapies an urgent necessity. Great progress in molecular biology techniques and advances in transgenic animal development provide great opportunities for the study of RCM and other cardiovascular diseases encountered in clinical patients.... Our laboratory is among the first to generate transgenic mouse models of RCM based on cardiac troponin I (cTnI) missense mutations. In this study, transgenic mice that suffer from RCM have been generated to understand the factors behind the diastolic dysfunction associated with that myocardial disease.... The information obtained from this study allows a better understanding of the role of troponin in RCM and the factors behind the physiopathology of the disease. It will also offer a therapeutic strategy taking into account the physiological characteristic of RCM.