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Published on: November 4, 2015
Expression of TRPM6 and TRPM7 in the preterm piglet heart
Elizabeth M Forbes1,2, Bhavisha A Bakrania2, Sarah E Steane3
1Queensland Children's Hospital, Brisbane, QLD, Australia.
Insights
Male preterm piglets show immature cardiac calcium handling due to lower TRPM7 expression, increasing their risk. TRPM7 may be a target to improve heart function in neonates.
Area of Science:
- Cardiovascular Physiology
- Neonatal Medicine
- Molecular Biology
Background:
- Preterm infants face high risks of death and disability, partly due to cardiovascular instability.
- Immature cardiac calcium handling in preterm neonates may impair myocardial contractility and cardiac output.
- TRPM6 and TRPM7 cation channels are potential regulators of neonatal cardiac calcium.
Purpose of the Study:
- To investigate TRPM6 and TRPM7 mRNA expression in piglet hearts during late gestation.
- To determine the influence of sex, maternal glucocorticoids, and birth transition on TRPM6/TRPM7 expression.
- To explore TRPM7 as a potential therapeutic target for neonatal cardiac dysfunction.
Main Methods:
- RT-qPCR was used to measure TRPM6 and TRPM7 mRNA expression in piglet ventricular tissues.
- Tissues were collected from piglets at various gestational ages, including preterm and term neonates.
- Experimental groups included cesarean-delivered and spontaneously born piglets, with and without maternal glucocorticoid exposure.
Main Results:
- Male piglets exhibited significantly lower left ventricular TRPM7 expression than females across gestational ages.
- TRPM7 expression increased postnatally in term piglets (at 6h vs. birth) but not in preterm piglets without glucocorticoid exposure.
- Maternal glucocorticoid treatment in preterm piglets led to increased postnatal TRPM7 expression in the right ventricle.
Conclusions:
- Male preterm piglets may possess immature myocardial calcium handling, contributing to adverse outcomes.
- The postnatal increase in TRPM7 expression observed in term infants is deficient in preterm neonates.
- TRPM7 modulation presents a potential novel strategy for enhancing cardiac function in preterm infants.
Abstract:
Preterm infants are at increased risk of death and disability, and cardiovascular instability after birth is a contributing factor. Immaturity of calcium handling in the preterm heart may limit myocardial contractility and cardiac output. Two transmembrane cation channels, TRPM6 and TRPM7, may regulate intracellular cardiac calcium in the neonatal period. The aim of this study was to determine TRPM6 and TRPM7 mRNA expression in piglet hearts in late gestation, and the effects of sex, maternal glucocorticoids, and the transition to extrauterine life. Left and right ventricular tissue was collected at a range of gestational ages from cesarean delivered piglets at birth and at 6 h old. Additional groups included piglets exposed to maternal glucocorticoid treatment and spontaneously born term piglets at 12-24 h old. TRPM6 and TRPM7 mRNA expression was measured using RT-qPCR. Males had significantly lower TRPM7 expression in the left ventricle across all gestational ages compared to females. At term, both ventricles had higher TRPM7 expression at 6 h old than at birth. In preterm piglets, TRPM7 expression only increased postnatally in the right ventricle following maternal glucocorticoid exposure. At 12-24 h old, TRPM7 expression in both ventricles was lower than levels in 6 h old term Caesar piglets (113 days). Male preterm piglets may have immature myocardial Ca2+ handling and this could contribute to their poorer outcomes. Increased TRPM7 expression is the mature response to birth that is missing in preterm neonates. TRPM7 could serve as a novel target to improve cardiac function in preterm neonates.
