Anti-angiogenic therapy prevents the development of asthma*1

Abstract Rationale Several studies have suggested the potential role of angiogenesis in the development of asthma. However, the precise mechanisms remain unclear. The aim of this study was to clarify the role of VEGF, a major angiogenic factor, in OVA-induced murine asthma model. Furthermore, we investigated whether anti-angiogenic therapy could prevent the development of asthma. Methods Female BALB/c mice were sensitized to OVA by intraperitoneal injections on day 1 and 8. Starting on day 18, they were exposed to aerosols of OVA for three consecutive days. Murine Endostatin, a potent anti-angiogenic factor, was given twice a day on days 18-21. Physiologic(plethysmography) and pathologic analysis was performed on day 22. Results VEGF positive cells around the airways and VEGF level in serum were markedly increased in this model (e.g., 35.7 ± 1.6 vs. 19.8 ± 3.8 pg/ml, OVA sensitized vs. PBS control, p=0.0014). Endostatin treatment significantly attenuated airway hyperresponsiveness (e.g., Penh, 12 mg/ml methacholine: 1.62 ± 0.19 vs. 0.88 ± 0.04, PBS vs. Endostatin, p=0.015) and pathologic changes of pulmonary allergic inflammation, resulted in decreased BAL eosinophilia (1.27 ± 0.23 x105 vs. 0.32 ± 0.08 x105/ml, p=0.0004) and blocked the production of OVA-specific IgE (29.5 ± 6.5 vs. 5.1 ± 1.1 mg/ml, p=0.028). Conclusions Angiogenesis plays a pivotal role in the development of acute asthma, and our data demonstrate for the first time that anti-angiogeneic, endostatin, treatment may be a novel and promising strategy for clinical asthma.