Abstract:
BACKGROUND:The postnatal development of myofibrillar mechanics, a major determinant of heart function, is unknown in pediatric patients with tetralogy of Fallot and related structural heart defects. We therefore determined the mechanical properties of myofibrils isolated from right ventricular tissue samples from such patients in relation to the developmental changes of the isoforms expression pattern of key sarcomere proteins involved in the contractile process. METHODS AND RESULTS:Tissue samples from the infundibulum obtained during surgery from 25 patients (age range 15 days to 11 years, median 7 months) were split into half for mechanical investigations and expression analysis of titin, myosin heavy and light chain 1, troponin-T, and troponin-I. Of these proteins, fetal isoforms of only myosin light chain 1 (ALC-1) and troponin-I (ssTnI) were highly expressed in neonates, amounting to, respectively, 40% and 80%, while the other proteins had switched to the adult isoforms before or around birth. ALC-1 and ssTnI expression subsequently declined monoexponentially with a halftime of 4.3 and 5.8 months, respectively. Coincident with the expression of ssTnI, Ca(2+) sensitivity of contraction was high in neonates and subsequently declined in parallel with the decline in ssTnI expression. Passive tension positively correlated with Ca(2+) sensitivity but not with titin expression. Contraction kinetics, maximal Ca(2+)-activated force, and the fast phase of the biphasic relaxation positively correlated with the expression of ALC-1. CONCLUSIONS:The developmental changes in myofibrillar biomechanics can be ascribed to fetal-to-adult isoform transition of key sarcomeric proteins, which evolves regardless of the specific congenital cardiac malformations in our pediatric patients.
journal_name
J Am Heart Assocjournal_title
Journal of the American Heart Associationauthors
Elhamine F,Iorga B,Krüger M,Hunger M,Eckhardt J,Sreeram N,Bennink G,Brockmeier K,Pfitzer G,Stehle Rdoi
10.1161/JAHA.116.003699subject
Has Abstractpub_date
2016-06-27 00:00:00issue
6issn
2047-9980pii
JAHA.116.003699journal_volume
5pub_type
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