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Published on: May 5, 2018
Prenatal exposure to carbon monoxide delays postnatal cardiac maturation
Laura Sartiani1, Francesca Stillitano, Cristina Luceri
1Centro Interuniversitario di Medicina Molecolare e Biofisica Applicata (C.I.M.M.B.A.), University of Firenze, Firenze, Italy.
Insights
Prenatal exposure to carbon monoxide (CO), a component of cigarette smoke, disrupts infant heart development. This study reveals molecular and functional changes in rat hearts, potentially increasing arrhythmia risk.
Area of Science:
- Cardiovascular Physiology
- Developmental Biology
- Toxicology
Background:
- Maternal smoking during pregnancy is linked to impaired infant cardiovascular autonomic maturation.
- Prenatal exposure to carbon monoxide (CO), a cigarette smoke component, has been shown to delay postnatal electrophysiological maturation of rat ventricular myocytes.
- This delay may predispose newborns to life-threatening arrhythmias.
Purpose of the Study:
- To comprehensively investigate the developmental molecular abnormalities in the rat heart caused by prenatal CO exposure.
- To correlate molecular changes with functional alterations in cardiac maturation.
- To assess the impact of prenatal CO on the expression of f-current, an electrophysiological marker of immature cardiac phenotype.
Main Methods:
- Prenatal exposure of rats to 0 (control) or 150 p.p.m. CO.
- Microarray analysis of rat ventricular tissue at postnatal days 4, 7, and 20.
- Differential gene expression and biological pathway analysis using Newton's approach and GENMAPP/MAPPFinder.
- Real-time RT-PCR with TaqMan probes.
- Patch-clamp electrophysiology to measure I(f) in isolated ventricular cardiomyocytes.
Main Results:
- Prenatal CO exposure significantly altered genes and pathways controlling cell cycle and excitation-contraction coupling in the developing rat heart.
- Cardiomyocytes from 7-day-old CO-exposed rats showed significant downregulation of mRNA for key sarcomeric proteins, transporters (Ca(2+) transporting ATPase), and enzymes (aldolase).
- The molecular and functional expression of f-channels, a marker of fetal ventricular phenotype, was transiently increased by 200% in CO-exposed rats compared to controls.
Conclusions:
- Prenatal CO exposure induces significant molecular and functional changes in cardiac development.
- These alterations, particularly the delayed maturation indicated by f-channel expression, may underlie the increased susceptibility to arrhythmias.
- The study provides crucial insights into the mechanisms of cardiac maturation impairment by prenatal exposure to smoking toxicants like CO.
Abstract:
Prenatal exposure to toxicants, such as maternal smoking, may impair cardiovascular autonomic maturation in infants. We recently showed that exposure of pregnant rats to a mild concentration of carbon monoxide (CO), a component of cigarette smoke, delays postnatal electrophysiological maturation of ventricular myocytes from newborns rats, likely predisposing to life-threatening arrhythmias. To get a comprehensive view of developmental molecular abnormalities induced, at cardiac level, by prenatal CO exposure, we used microarray analysis approach on the rat heart at 4, 7 and 20 days postnatal life. The relationship between molecular and functional alterations was investigated by assessing the ventricular expression of f-current, an electrophysiological marker of immature cardiac phenotype. Rats were prenatally exposed to 0 (CTR) or 150 p.p.m. CO and mRNA obtained from ventricular samples. Differential analysis and biological pathway analysis of microarray data were performed by using Newton's approach and the GENMAPP/MAPPFinder, respectively. The real-time RT-PCR reactions were performed by TaqMan probe-based chemistry. Freshly isolated patch-clamped ventricular cardiomyocytes were used to measure I(f). Genes and pathways controlling cell cycle and excitation-contraction coupling were significantly modified in CO-exposed rats. The higher effect was observed in cardiomyocytes harvested from 7-day-old rats, in which mRNA expression for crucial sarcomeric proteins (myosin and actin subunits, troponin I), transporters (Ca(2+) transporting ATPase) and enzymes (aldolase) were significantly downregulated. Accordingly, the molecular and functional expression of f-channels, which represents a marker of fetal ventricular phenotype, was transiently greater in CO-exposed rats (+200%) than in control ones. In conclusion, our study provides new insights into the molecular and functional mechanisms underlying cardiac maturation and its impairment by prenatal exposure to toxic components of smoking, such as CO.
