The hypoplastic heart in congenital diaphragmatic hernia: reduced expression of basic fibroblast growth factor and platelet-derived growth factor

Newborn infants with congenital diaphragmatic hernia (CDH) still have high mortality. Recently, the possible role of a cardiac maldevelopment in the h igh mortality has been suggested. Human and animal studies have demonstrate d that heart weight is significantly reduced in the presence of CDH. Basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF) a re pleiotropic regulatory peptides that are expressed in myocardium in prec ise developmental and spatial programs. PDGF and bFGF both stimulate cardia c growth by inducing cell proliferation and stimulating the synthesis of ex tracellular matrix. The aim of this study was to investigate the presence o f 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 p regnant rats following administration of 100 mg nitrofen on day 9.5 of gest ation (term 22 days). In control animals the same dose of olive oil was giv en without nitrofen. Cesarean section was performed on day 21 of gestation. The fetuses were divided in two groups: normal controls (n = 8) and nitrof en-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 R NA and a reverse transcription-polymerase chain reaction (RT-PCR) was perfo rmed to evaluate mRNA expression of bFGF and PDGF. The heart/body weight ra tio (HBWR) and DNA content were significantly decreased (P < 0.01) in CDE-I 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, a nd protein content ill the CDH heart indicates that the heart is hypoplasti c in nitrofen-induced left CDH. The downregulation of bFGF and PDGF gene ex pression in the CDH heart suggests that these regulating peptides may play an important role in the genesis of cardiac hypoplasia in CDH.