Gene expression of vascular endothelial growth factor and its receptors and angiogenesis in bronchial asthma

Background: Angiogenesis is a feature of airway remodeling in bronchial asthma, The mechanism responsible for this angiogenesis is unknown. Vascular endothelial growth factor (VEGF) is a potent inducer of endothelial cells, which may contribute to chronic inflammation and angiogenesis, Objective: We sought to investigate the molecular mechanisms underlying increased vascularity, and we examined the mRNA expression of VEGF and its receptors (flt-1 and flk-1) within bronchial biopsy specimens from asthmatic patients and normal control subjects. Methods: Endobronchial biopsy specimens were examined immunocytochemically by staining with anti-type IV collagen mAb to evaluate vessel density by using computer-assisted image analysis. Specimens were also analyzed for the presence of the mRNAs of VEGF and its receptors with in situ hybridization, Results: The extent of airway vascularity was increased in asthmatic subjects compared with that in control subjects (P < .01). Asthmatic subjects exhibited a greater expression of VEGF, flt-1, and flk-1 mRNA(+) cells in the airway mucosa compared with that in control subjects (P < .001 for each comparison). The degree of vascularity was associated with the number of VEGF, flt-1, and flk-1 mRNA(+) cells. Numbers of cells expressing VEGF mRNA inversely correlated with airway caliber (r = -0.83, P < .01) and airway hyperresponsiveness (r = -0.97, P < .001). Colocalization studies showed that macrophages, eosinophils, and CD34(+) cells were the major sources or VEGF; CD34(+) cells, macrophages, and T cells expressed both flt-1 and flk-1, Conclusion: These findings provide evidence that VEGF may play an important role in angiogenesis and subsequent airway remodeling in bronchial asthma.