Abstract
The cysteinyl leukotrienes have been implicated in the pathophysiology of asthma by way of multiple mechanisms, including mucus hypersecretion, increased microvascular permeability, ciliary activity impairment, inflammatory cell recruitment, edema, and neuronal dysfunction. Vascular endothelial growth factor (VEGF; also known as vascular permeability factor) is one of the most potent proangiogenic cytokines, and it plays a central role in mediating the process of angiogenesis. VEGF also increases vascular permeability so that plasma proteins can leak into the extravascular space, which leads to edema and profound alterations in the extracellular matrix. We have used a murine model of asthma to examine the possible pathophysiological mechanisms regarding the increased vascular permeability of cysLTs in asthma.
Results: These mice develop the following typical pathophysiological features in the lungs: increased numbers of inflammatory cells, airway hyper-responsiveness, increased vascular permeability, and increased levels of VEGF. Administration of cysteinyl leukotriene receptor antagonists reduced all these pathophysiological symptoms.
Conclusion: These results suggest that cysteinyl leukotriene receptor antagonists regulate vascular permeability by reducing VEGF expression.