Ghrelin Decreases Angiogenesis, HIF-1α and VEGF Protein Levels in Chronic Hypoxia in Lung Tissue of Male Rats.
OBJECTIVE
Hypoxia is a condition of decreased availability of oxygen. When cells are exposed to a low oxygen environment, they impel the hypoxia responses to adapt to new situation. The hypoxia response leads to the activation of various cellular signaling pathways. The aim of this study was to evaluate the effect of ghrelin on angiogenesis, Hypoxia-Inducible-Factor-1α (HIF-1) and Vascular endothelial growth factor (VEGF) levels in normobaric hypoxia situation.


METHODS
Twenty four animals were divided into 4 groups (n=6): control (C), ghrelin (Gh), hypoxia (H), and hypoxic animals that received ghrelin (H+Gh). Hypoxia (11%) was induced by an Environmental Chamber System GO2 Altitude. Animals in ghrelin groups received a subcutaneous injection of ghrelin (150 μg/kg/day) for 14 days.


RESULTS
Our results showed that hypoxia significantly (p<0.05) increased angiogenesis without any significant changes on HIF-1 and VEGF levels, whereas ghrelin significantly (p<0.05) decreased angiogenesis, expression of HIF-1 and VEGF in this condition. Ghrelin administration did not show any significant changes in normal conditions.


CONCLUSIONS
Ghrelin had no effect on angiogenesis, expression of HIF-1 and VEGF in normal oxygen conditions but it reduced angiogenesis process in lung tissue with reducing the level of HIF and VEGF in hypoxic condition. Therefore, effect of ghrelin on angiogenesis could be related to blood oxygen level.
Tuberculosis and Lung Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Fariba
F
Mirzaei Bavil
Tuberculosis and Lung Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Mohammad Reza
MR
Alipour
Tuberculosis and Lung Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Rana
R
Keyhanmanesh
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Alireza
A
Alihemmati
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Rafigheh
R
Ghiyasi
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Gisou
G
Mohaddes
Ghrelin; HIF-1α; Normobaric hypoxia; VEGF