Open AccessPostnatal Development of Right Ventricular Myofibrillar Biomechanics in Relation to the Sarcomeric Protein Phenotype in Pediatric Patients with Conotruncal Heart Defects
Author(s) -
Elhamine Fatiha,
Iorga Bogdan,
Krüger Martina,
Hunger Mona,
Eckhardt Jan,
Sreeram Narayanswami,
Bennink Gerardus,
Brockmeier Konrad,
Pfitzer Gabriele,
Stehle Robert
Publication year - 2016
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.116.003699
Subject(s) - myofibril , titin , myosin , medicine , troponin , sarcomere , troponin i , heart development , gene isoform , actin , tetralogy of fallot , myofilament , cardiology , troponin t , contractility , endocrinology , microbiology and biotechnology , heart disease , myocyte , biology , biochemistry , myocardial infarction , gene , embryonic stem cell
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.