VEGF, Angiopoietin-1 and -2 in Bronchial Asthma: New Molecular Targets in Airway Angiogenesis and Microvascular Remodeling
Affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, 1-4-3, Asahi-machi, Abenoku, Osaka, 545-8585, Japan.
Airway angiogenesis and microvascular remodeling are known features of bronchial asthma, but the mechanisms of these structural alterations are just beginning to be elucidated. Vascular endothelial growth factor (VEGF), one of the most potent angiogenic factors, stimulates endothelial cell proliferation and induces the angiogenesis. Recently, considerable attentions have been devoted to the physiological roles of angiopoietin (Ang)-1 and -2 as regulatory factors of VEGF. Ang-1 has been shown to induce the migration and sprouting of endothelial cells, and coexpression of Ang-1 and VEGF enhanced angiogenesis. In the presence of high levels of VEGF, Ang-2 also promotes rapid increase in capillary diameter, remodeling of the basal lamina, proliferation and migration of endothelial cells, and stimulates sprouting of new blood vessels. Thus, VEGF, Ang-1 and -2 may play complementary and coordinated roles in airway angiogenesis and microvascular remodeling, and these structural changes are potentially reversible by therapeutic intervention. The scope of the present review is to discuss from a clinical point of view the potential interactions between VEGF and angiopoietins in the asthmatic airways, and focus on the therapeutic implications targeting for these angiogenic factors. Recently, there is an increasing number of patents which have been focused on the inhibitors of VEGF action. These inhibitors are directed towards the receptors of VEGF or intracellular substrates for the receptors. We will also discuss several patents regarding inhibitors of VEGF action in the present review.
Keywords: Bronchial asthma, angiogenesis, microvascular remodeling, vascular endothelial growth factor, angiopoietin-1, angiopietin-2, Tie-2
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