The Change of Expression of Troponin T and I Isoforms in the Failing Myocardium of Rat after Myocardial Infarction

Kim, Young Dae; Kim, In Hoo; Kim, Jong Seong; Kim, Hyo Soo; Kim, Sang Hyun; Sohn, Dae Won; Kim, Cheol Ho; Oh, Byung Hee; Lee, Myoung Mook; Park, Young Bae; Choi, Yun Shik; Seo, Jung Don; Lee, Young Woo; Potter, James D

Abstract

BACKGROUND
Contractile dysfunction of rat myocardium in postinfarction remodeling is characterized by decreased response of myofilament both to calcium(Ca++) and adrenergic stimuli. This study tested the hypothesis that above alterations may be linked to molecular switches among the isoforms of troponin T and troponin I, the major regulators of myocardial responsiveness.
METHODS
Using Sprague-Dawley rat as a model, myocardiums of fetal heart, 1 day postnatal heart, normal adult heart(n=4), and non-infarcted area of postinfarction heart(n=4, 3 months after left coronary artery ligation, mean LVEDP=21.4mmHg) were studied. For the detection on molecular switches, western blotting and semiquantitative RT-PCR were employed.
RESULTS
Immunoblotting of rat myocardium showed normal developmental isoform switch of troponin protein. There was distinct isoform patterns specific for postinfarction rat heart. The postinfarction myocardium developed a marked increase in the fetal isoform and marked decrease in the adult isoform of troponin T, resulting in the reversed ratio of fetal/adult cardiac troponin T isoform(normal adult rat=0.60+/-0.1 vs postinfarction rat=1.79+/-0.15, p<0.01). Also, the postinfarction heart showed approximately 20% decrease in the amount of adult troponin I isoform. In RT-PCR experiments, the postinfarction hearts were characterized by increased amplification of fetal troponin R isoform cDNA(fetal troponin R/GAPDH ; normal adult rat=0.22, postinfarction rat=0.84). However, there was no siginificant difference in the amplification of troponin I cDNA between normal and postinfarction heart.
CONCLUSION
These experimental findings indicate that there are molecular switches operative among the regulatory protein troponin T and I in the rat myocardium with development of postianfarction heart failure.