Vascular endothelial growth factor expression in heart of rats exposed to hypobaric hypoxia: differential response between mRNA and protein.

Abstract

This study investigated the role of vascular endothelial growth factor (VEGF) in the neoangiogenesis induced in heart in response to hypoxia. The time-course of adaptive changes in capillary supply, expression of VEGF mRNA and protein was studied in right (RV) and left ventricles (LV) of rats exposed to hypobaric hypoxia during 1-25 days (barometric pressure = 505 hPa). VEGF mRNA levels encoding for VEGF 188 and 164 isoforms were measured by reverse transcription-polymerase chain reaction (RT-PCR) and VEGF protein was determined by Western blotting. Relative RV weight (i.e., weight of RV related to body weight) increased with hypoxia and was 102% higher than in controls after 15 days of exposure (P < 0.01), while relative LV weight remained unaltered. A rapid and transient increase in VEGF 188 mRNA occurred after 1 day of hypoxia in LV (P < 0.05). Thereafter, a delayed increase in VEGF 188 mRNA expression occurred in RV (ANOVA, P < 0.001). By day 18, VEGF 188 mRNA level was higher in hypoxic than in control rats (P < 0.005) and then decreased to base line levels. Hypoxia did not affect the expression of VEGF 164 mRNA neither in LV nor in RV. One of the main results was that these hypoxia-induced alterations in VEGF transcripts were not followed by associated increase in VEGF protein. These results suggest that capillary growth observed in RV after prolonged exposure to ambient hypoxia likely results from other molecular mechanisms than VEGF.