Oxidative stress due to hypoxia/reoxygenation induces angiogenic factor VEGF in adult rat myocardium: possible role of NFkappaB.
BACKGROUND
Oxidative stress, as exerted by free radicals within biological systems, is known to exert numerous physiological and pathological effects on the cardiovascular system. Short-term exposure to environmental conditions such as low oxygen tension can cause such oxidative stress in vivo through inhalational hypoxia/reoxygenation. In this report the effects of different durations of hypoxia were investigated on myocardial protein expression of vascular endothelial growth factor (VEGF). a major angiogenic growth factor, and also explore the possible modulatory role of transcription factor NFkappaB on such expression.


METHODS
Forty eight male Sprague-Dawley rats (300 g b.w.) were randomly divided into four groups and subjected to either 1, 2 or 4 h of systemic normobaric hypoxemic hypoxia (10+/-0.4% O2) in an anesthesia chamber, or to 4 h of normoxia (ambient 20.9+/-0.4% O2) to time-match the maximal hypoxic duration. All rats were then kept under normoxic conditions. Rats were sacrificed and hearts harvested either after 2 h for later electrophoretic mobility gel shift assay for NFkappaB, or after 24 h for later Western blot analysis for VEGF.


RESULTS
Western blot analysis for VEGF revealed significantly elevated protein expression (2.4-fold compared to baseline control) in the I h group. This elevated level persisted in the 2 and 4 h groups as well. Two hours post-hypoxia gel shift assay for NFkappaB indicated significant nuclear translocation and DNA binding of this transcription factor in the 1 and 2 h groups, with moderate decrease in the 4 h group.


CONCLUSIONS
In vivo oxidative stress caused by systemic inhalational hypoxemic hypoxia increases cardiac VEGF protein expression and may trigger myocardial angiogenesis. The results suggest that NFkappaB modulates such an effect.
Sasaki
H
H
Department of Surgery, University of Connecticut School of Medicine, Farmington 06030-1110, USA.
Ray
P S
PS
Zhu
L
L
Galang
N
N
Maulik
N
N
D000818:Animals; D015153:Blotting, Western; D004247:DNA / Q000378:metabolism; D016228:Endothelial Growth Factors / Q000096:biosynthesis*; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D008222:Lymphokines / Q000096:biosynthesis*; D008297:Male; D023421:Models, Animal; D017682:Myocardial Stunning / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D016328:NF-kappa B; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D004247:DNA