Diaphragmatic angiogenic growth factor mRNA responses to increased ventilation caused by hypoxia and hypercapnia

Abstract

This study investigates the effect of increased ventilation on the expression of messenger ribonucleic acid (mRNA) levels of vascular endothelial growth factor (VEGF), basic ®broblast growth factor (bFGF) and transforming growth factorb 1 (TGF-b 1 ) in the diaphragm of intact, awake, spontaneously breathing rats, compared with responses in paralysed, mechanically-ventilated animals at similar blood gas and ventilatory levels.Four groups of intact, rats were studied in a body box, each group breathing one of four gases: room air, 12% oxygen (O 2 ), 5% carbon dioxide (CO 2 ), or 12% O 2 +5% CO 2 for 1 h. Another 4 groups of paralysed, mechanically-ventilated animals were matched for arterial blood gas and ventilatory level.The results showed that VEGF mRNA abundance was increased three-fold and that of bFGF 1.5-fold when 12% O 2 +5% CO 2 were breathed, but TGF-b 1 did not change. A signi®cant linear relationship of VEGF and bFGF mRNA to minute ventilation was observed in awake animals (r=0.98, p<0.02 and r=0.87, p<0.03, respectively). The paralysed, mechanically-ventilated animals showed no mRNA increases for any probe. Systemic hypoxia had no additional effect on VEGF or bFGF levels in the diaphragm.It was concluded that messenger ribonucleic acid for vascular endothelial growth factor and basic ®broblast growth factor in the diaphragm rises signi®cantly as a result of active ventilation and not due to blood gas/pH changes or to passive muscle shortening per se. Eur Respir J 2001; 17: 681±687.

Time-based gene expression programme following diaphragm injury in a rat model

“…Diaphragm bFGF expression is not well known. It is enhanced by hypoxiainduced hyperventilation [44] and is decreased in mdx mice [45]. The current authors found that the rise in bFGF mRNA lasted 96 h PI, confirming the involvement of bFGF in the diaphragmatic repair programme.…”

Vascular endothelial growth factor in pleural effusions of different origin

“…Other results suggest that bacterial pathogens induce VEGF release in mesothelial cells and alter mesothelial permeability, leading to protein exudation in empyema [20]. Furthermore, VEGF mRNA has been described as being upregulated by increased ventilation caused by hypoxia or hypercapnia [21].…”

The immune response to resistive breathing

“…This might be important for the increased ventilation requirements of some elite athletes during athletic performance, although the benefit from additional specific respiratory muscle training is uncertain [7]. However, angiogenesis is even more important for the beneficial effects of rehabilitation programmes involving training of the respiratory muscles [8].…”

“…Recent data have shown that acute exercise upregulates the mRNA expression, while there is a graded response in the expression of mRNA of this angiogenic factor with the metabolic stress. Furthermore, it is demonstrated that mRNA for VEGF and bFGF in the diaphragm of rats rises significantly as a result of active increased ventilation due to hypoxia and/or hypercapnia, while no changes in mRNA levels were observed in paralysed, mechanically ventilated animals at similar arterial blood gases and ventilation levels [7,8]. However, there is evidence that resistive breathing upregulates mRNA for VEGF, but not for bFGF and TGF-b1 [9].…”