Changes in cardiac troponins with gestational age explain changes in cardiac muscle contractility in the sheep fetus

Abstract

The development of the adult cardiac troponin complex in conjunction with changes in cardiac function and cardiomyocyte binucleation has not been systematically characterized during fetal life in a species where maturation of the cardiomyocytes occurs prenatally as it does in the human. The aim of this study was to correlate the expression of each of the major adult troponin isoforms (T, I, and C) during late gestation (term of 150 days) to changes in both Ca(2+) sensitivity and maximum Ca(2+)-activated force of the contractile apparatus and the maturation of cardiomyocytes. The percentage of mononucleated cardiomyocytes in the right ventricle decreased with gestational age to 46% by 137-142 days of gestation. The length of binucleated cardiomyocytes did not change with gestational age, but the length of binucleated cardiomyocytes relative to heart weight decreased with gestational age. There was no change in the expression of adult cardiac troponin T with increasing gestation. The contractile apparatus was significantly more sensitive to Ca(2+) at 90 days compared with either 132 or 139 days of gestation, consistent with an ∼30% increase in the expression of adult cardiac troponin I between 90 and 110 days of gestation. Maximum Ca(2+)-activated force significantly increased from 90 days compared with 130 days consistent with an increase of ∼40% in cardiac troponin C protein expression. These data show that increased adult cardiac troponin I and C protein expression across late gestation is consistent with reduced Ca(2+) sensitivity and increased maximum Ca(2+)-activated force. Furthermore, changes in cardiac troponin C, not I, protein expression track with the timing of cardiomyocyte binucleation.

Fetal cardiac muscle contractility decreases with gestational age: a color-coded tissue velocity imaging study

“…Recent findings demonstrate changes in cardiac muscle contractility in the sheep fetus explained by changes in cardiac troponins with gestational age [1]. Contractility is here correlated with the process of cardiomyocyte binucleation, a transition from mono- to binucleated cardiomyocytes that, as in the human fetus, occur before birth.…”

“…Rather a change in elastic properties and contractility are plausible explanations for this phenomenon. Most likely, as illustrated in the sheep fetus, contractility is correlated with the process of cardiomyocyte binucleation [1], a transition from mono- to binucleated cardiomyocytes that, as in the human fetus, occur before birth.…”

“…We are presently evaluating this method in high risk pregnancies. It is tempting to speculate that myocardial maturation is critical in preparing the fetal heart to cope with the intrauterine environment and the increased demand at birth and to successfully adapt to extra uterine life [1,17]. …”

“…This is, as illustrated in the sheep fetus, most likely due to changes in the troponin system before and during cardiomyocyte binucleation [1]. …”

Activation of IGF‐2R stimulates cardiomyocyte hypertrophy in the late gestation sheep fetus

“…Overall, our findings suggest that cardiac IGF‐2R activation may alter important regulators of cardiac contractility and relaxation. It is possible that these changes precede the onset of chronic heart failure and this also requires further investigation, for example investigating cardiac Ca 2+ sensitivity for the contractile apparatus and maximum Ca 2+ ‐activated force (Posterino et al 2011).…”