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The hypoplastic heart in congenital diaphragmatic hernia: reduced expression of basic fibroblast growth factor and
1Children's Research Centre, Our Lady's Hospital for Sick Children, Crumlin, Dublin, Ireland.
Insights
Congenital diaphragmatic hernia (CDH) in rat models is linked to heart hypoplasia. Reduced expression of basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF) may contribute to this cardiac maldevelopment.
Area of Science:
- Developmental biology
- Cardiovascular research
- Teratology
Background:
- Congenital diaphragmatic hernia (CDH) is associated with high infant mortality.
- Cardiac maldevelopment is increasingly recognized as a contributing factor to CDH mortality.
- Growth factors like basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF) are crucial for cardiac development.
Purpose of the Study:
- To investigate cardiac hypoplasia in a rat model of nitrofen-induced CDH.
- To examine the role of bFGF and PDGF in the genesis of cardiac hypoplasia in CDH.
Main Methods:
- Nitrofen was administered to pregnant rats to induce CDH in fetuses.
- Heart and body weights, RNA, DNA, and protein content were measured in control and CDH fetuses.
- Reverse transcription-polymerase chain reaction (RT-PCR) was used to assess bFGF and PDGF mRNA expression.
Main Results:
- CDH fetuses exhibited significantly decreased heart/body weight ratio (HBWR) and DNA content compared to controls.
- Reduced RNA and protein content were also observed in the hearts of CDH fetuses.
- mRNA expression of bFGF and PDGF was significantly downregulated in the CDH group.
Conclusions:
- The study demonstrates heart hypoplasia in nitrofen-induced CDH in rats.
- Downregulation of bFGF and PDGF gene expression suggests their critical role in CDH-associated cardiac hypoplasia.
- These findings highlight potential therapeutic targets for improving outcomes in CDH.
Abstract:
Newborn infants with congenital diaphragmatic hernia (CDH) still have high mortality. Recently, the possible role of a cardiac maldevelopment in the high mortality has been suggested. Human and animal studies have demonstrated that heart weight is significantly reduced in the presence of CDH. Basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF) are pleiotropic regulatory peptides that are expressed in myocardium in precise developmental and spatial programs. PDGF and bFGF both stimulate cardiac growth by inducing cell proliferation and stimulating the synthesis of extracellular matrix. The aim of this study was to investigate the presence of heart hypoplasia in nitrofen-induced CDH in rats and the role of specific tissue growth factors (bFGF and PDGF) in its genesis. CDH was induced in pregnant rats following administration of 100 mg nitrofen on day 9.5 of gestation (term 22 days). In control animals the same dose of olive oil was given without nitrofen. Cesarean section was performed on day 21 of gestation. The fetuses were divided in two groups: normal controls (n = 8) and nitrofen-induced CDH (n = 8). Total RNA, DNA, and soluble proteins were extracted from the heart in each group and measured. mRNA was extracted from total RNA and a reverse transcription-polymerase chain reaction (RT-PCR) was performed to evaluate mRNA expression of bFGF and PDGF. The heart/body weight ratio (HBWR) and DNA content were significantly decreased (P < 0.01) in CDH animals compared to controls. RNA and protein content were also reduced in CDH. The expression of bFGF and PDGF mRNA was significantly reduced in the CDH group compared to controls (P < 0.01). The decreased HBWR, DNA, RNA, and protein content in the CDH heart indicates that the heart is hypoplastic in nitrofen-induced left CDH. The downregulation of bFGF and PDGF gene expression in the CDH heart suggests that these regulating peptides may play an important role in the genesis of cardiac hypoplasia in CDH.