TROPONIN-T MESSENGER-RNA AND PROTEIN ISOFORMS IN THE HUMAN LEFT-VENTRICLE - PATTERN OF EXPRESSION IN FAILING AND CONTROL HEARTS

L. Messnard-Rouiller, J.-J. Mercadier, G. Butler-Browne, M. Heimburger , D. Logeart, P.D. Allen and F. Samson. Troponin T mRNA and Protein Is oforms in the Human Left Ventricle: Pattern of Expression in Failing a nd Control Hearts. Journal of Molecular and Cellular Cardiology (1997) 29, 3043-3055. We and others have previously cloned several cDNAs of human cardiac troponin T (cTnT), demonstrating the multiplicity of cTn T isoforms in the human heart. Four of them named cTnT1, 2, 3, and 4 r esult from a combinatorial alternative inclusion of 30- and 15-nucleot ides in the 5' coding region of the cDNAs. In failing human ventricles , increased expression of fetal-type splicing products in the 5' regio n, one of them corresponding to cTnT1. To clarify this issue, we exami ned the accumulation of the 4 cTnT mRNA and protein species in left ve ntricular specimens at the time of heart transplantation, and in contr ol left ventricular samples using RNase protection and Western blottin g. In all samples, cTnT3 was the major mRNA isoform. cTnT4 a minor iso form while cTnT1 and cTnT2 mRNAs were present but barely detectable. A t the protein level, cTnT3, 4 and 1 were detected with the same relati ve abundance as that seen at the mRNA level. In addition, we detected a fourth TnT species of very low abundance corresponding either to a s keletal or to a ''short'' cardiac TNT isoform. Compared to controls, i ncreased levels of cTnT4 mRNA and protein were detected in only half t he failing ventricles independently of the cause of failure, suggestin g that this increase may not be a general characteristic of left ventr icular failure but instead could be related to stress. Unexpectedly, w e found a decrease in cTnT1 protein expression in all failing ventricu lar samples studied, compared to controls.