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Perinatal profile of ventricular overload markers in congenital diaphragmatic hernia

Maria João Baptista1, Cristina Nogueira-Silva, José Carlos Areias

  • 1Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.

Journal of Pediatric Surgery
|April 15, 2008
PubMed

Insights

Congenital diaphragmatic hernia (CDH) in pups causes significant changes in right ventricle (RV) gene expression after birth. These molecular alterations involve B-type natriuretic peptide (BNP), angiotensinogen, and endothelin-1 (ET-1) pathways.

Area of Science:

  • Cardiovascular Research
  • Developmental Biology
  • Molecular Genetics

Background:

  • Congenital diaphragmatic hernia (CDH) is linked to pulmonary hypertension, increasing right ventricle (RV) afterload and potentially impairing cardiac function.
  • Pulmonary vascular alterations in perinatal hemodynamics are not well understood in CDH.
  • Ventricular pressure overload is known to upregulate myocardial gene expression of B-type natriuretic peptide (BNP) and components of the renin-angiotensinogen and endothelin-1 (ET-1) systems.

Purpose of the Study:

  • To evaluate perinatal myocardial gene expression of BNP, angiotensinogen, and ET-1 in a nitrofen-induced CDH rat model.
  • To investigate the association between ventricular pressure overload and specific gene expression in the developing heart.

Main Methods:

  • Utilized a nitrofen-induced CDH rat model.
  • Collected myocardial samples from the RV and left ventricle (LV) of control, nitrofen-exposed, and CDH fetuses and pups at various gestational ages (15.5-21.5 days) and after birth.
  • Quantified messenger RNA (mRNA) levels of BNP, angiotensinogen, and ET-1 using molecular techniques.

Main Results:

  • Perinatal expression of BNP, angiotensinogen, and ET-1 mRNA showed daily variations in the RV and LV of the control group.
  • During gestation, BNP and angiotensinogen mRNA expression oscillated significantly in nitrofen-exposed fetuses compared to controls, with no significant differences between nitrofen and CDH groups.
  • Postnatally, a significant increase in the expression of all studied genes was observed exclusively in the RV of CDH pups.

Conclusions:

  • Perinatal myocardial gene expression of BNP, angiotensinogen, and ET-1 exhibits prenatal variations in both nitrofen-exposed and control pups.
  • Congenital diaphragmatic hernia (CDH) is associated with significant molecular alterations specifically in the right ventricle (RV) after birth.
Abstract

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