Diminished Pulmonary Expression of Hypoxia-Inducible Factor 2-<I>α</I>, Vascular Endothelial Growth Factor and Hepatocyte Growth Factor in Chickens Exposed to Chronic Hypobaric Hypoxia

Abstract

In a view to explore blood vessels neo formation as a possible adaptive response to hypobaric hypoxia in the chicken lung, mRNA expression of the following genes was examined: hypoxia inducible factor-1α (HIF-1α) and -2α (HIF-2α), vascular endothelial growth factor (VEGF), receptors for VEGF (Flk-1 and Flt-1), hepatocyte growth factor (HGF) and its receptor (HGFR), epidermal growth factor (EGF) and its receptor (EGFR). The molecular regulation of these genes remains completely unknown in these conditions. One group of birds was exposed to relative normoxia and the other group, to hypobaric hypoxia. Comparisons were made among non-pulmonary hypertensive chickens under relative normoxic conditions (NHCN) and non-pulmonary hypertensive chickens (NHCH) and pulmonary hypertensive chickens (PHCH) under hypobaric hypoxic conditions, respectively. For HIF-2α, VEGF, Flk-1, HGF and HGFR genes, no statistical differences were found in the relative mRNA expression between PHCH and NHCH, but those were lower when compared to NHCN (P<0,05). For Flt-1 mRNA expression, a significant difference between NHCH and NHCN was noted (P<0.05), but relative mRNA expression in the lungs of PHCH did not show differences with findings in the lungs of NHCN or NHCH. HIF-1α and EGFR mRNA expression analysis indicated significant differences between NHCN and PHCH, but not between NHCH and PHCH. There was a general trend towards a lower mRNA expression of genes involved in the response to hypoxia and vascular proliferation in the lungs of chickens exposed to chronic hypoxia in PHCH and NHCH when compared with NHCN. These results show consistency with those registered in a parallel study which indicated a lower number of blood vessels with a diameter range ≥50-100 μm in the lungs of PHCH and NHCH when compared with observations obtained in NHCN.