TROPONIN-I GENE-EXPRESSION DURING HUMAN CARDIAC DEVELOPMENT AND IN END-STAGE HEART-FAILURE

Recent reports have demonstrated the presence of two isoforms of tropo nin I in the human fetal heart, namely, cardiac troponin I and slow sk eletal muscle troponin I. Structural and physiological considerations indicate that these isoforms would confer differing contractile proper ties on the myocardium, particularly on the phosphorylation-mediated r egulation of contractility by adrenergic agonists. We have investigate d the developmental expression of these isoforms in the human heart fr om 9 weeks of gestation to 9 months of postnatal life, using Western b lots revealed with troponin I antibodies to detect troponin protein is oforms and Northern blots to detect the corresponding mRNAs. The resul ts show the following: 1) Slow skeletal muscle troponin I is the predo minant isoform throughout fetal life. 2) After birth, the slow skeleta l isoform is lost, with cardiac troponin I being the only isoform dete ctable by 9 mouths of postnatal development. 3) The protein isoforms a nd their corresponding mRNAs follow the same pattern of accumulation, suggesting that the transition in troponin expression is regulated at the level of gene transcription. The developmental transition in tropo nin I isoform content has implications for contractility of the fetal and postnatal myocardium. We further analyzed right and left ventricul ar muscle samples from 17 hearts in end-stage heart failure resulting from pulmonary hypertension, ischemic heart disease, or dilated cardio myopathy. Cardiac troponin I mRNA remained abundant in each case, and slow skeletal muscle troponin I mRNA was not detectable in any of samp le. We conclude that alterations in troponin I isoform content do not therefore contribute to the altered contractile characteristics of the adult failing ventricle.