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Association of neonatal hypoxia with lasting changes in left ventricular gene expression: an animal model
Danny Del Duca1, Guoruey Wong, Phan Trieu
1Division of Cardiovascular Surgery, Montréal Children's Hospital-McGill University Health Centre, Montréal, Québec, Canada.
Insights
Neonatal hypoxia causes lasting changes in heart gene expression, impacting adult heart cell viability. This early-life condition may affect adult cardiovascular health and disease outcomes.
Area of Science:
- Cardiovascular Research
- Neonatal Physiology
- Gene Expression Analysis
Background:
- Pediatric cardiovascular surgery has improved survival for congenital heart disease.
- Adults with congenital heart disease still face significant surgical risks.
- Early-life hypoxemia may induce persistent cardiac gene expression changes.
Purpose of the Study:
- To investigate if early-life hypoxia causes lasting changes in gene expression in the developing heart.
- To determine if these gene expression changes persist into adulthood.
- To assess the physiological impact on the adult myocardium.
Main Methods:
- Microarray analysis of left ventricular tissue from neonatal and adult rats exposed to hypoxia.
- Real-time reverse transcriptase polymerase chain reaction to confirm gene expression changes.
- Isolation and comparison of left ventricular cardiomyocytes from adult rats.
Main Results:
- Significant changes in 1945 neonatal and 422 adult cardiac genes were observed.
- Hypoxia affected genes related to vascular remodeling, energy homeostasis, and apoptosis.
- Cardiomyocyte viability was significantly lower in adult rats exposed to neonatal hypoxia.
Conclusions:
- Neonatal hypoxia induces substantial left ventricular gene expression alterations in both young and adult rats.
- These persistent gene expression changes may have significant physiological consequences for the adult heart.
Objective:
Innovations in pediatric cardiovascular surgery have resulted in significant improvements in survival for children with congenital heart disease. In adults with such disease, however, surgical morbidity and mortality remain significant. We hypothesized that hypoxemia in early life causes lasting changes in gene expression in the developing heart and that such changes may persist into later life, affecting the physiology of the adult myocardium.
Methods:
Microarray expression analyses were performed with left ventricular tissue from 10- and 90-day-old rats exposed to hypoxia (inspired oxygen fraction 0.12) for the first 10 days after birth then subsequently reared in ambient air and with tissue from age-matched rats reared entirely in ambient air. Changes in expression of selected genes were confirmed with real-time reverse transcriptase polymerase chain reaction. Left ventricular cardiomyocytes were isolated from adult animals in both groups, and cellular morphology and viability were compared.
Results:
Microarray analyses revealed significant changes in 1945 and 422 genes in neonates and adults, respectively. Changes in genes associated with adaptive vascular remodeling and energy homeostasis, as well as regulation of apoptosis, were confirmed by real-time reverse transcriptase polymerase chain reaction. The viability of cardiomyocytes isolated from hypoxic animals was significantly lower than in those from control animals (36.7% +/- 13.3% vs 85.0% +/- 2.9%, P = .024).
Conclusions:
Neonatal hypoxia is associated with significant changes in left ventricular gene expression in both neonatal and adult rats. This may have physiologic implications for the adult myocardium.
