Abstract
Although largely distinct and seemingly unrelated, asthma and pulmonary arterial hypertension (PAH) have important pathological features in common, including inflammation, smooth muscle contraction and remodelling. We hypothesised that these common features could be explained by one shared mechanism of pathogenesis: activation of the transcription factor NFAT (nuclear factor of activated T-cells). If this concept is validated, it could lead to the introduction of novel therapeutic strategies against both lung disorders. In several experimental models, airway remodelling is accompanied by remodelling of smaller pulmonary arteries, validating the hypothesis of their similar pathogenesis. In addition, lungs of vasoactive intestinal peptide (VIP) knockout mice express airway hyperresponsiveness with airway inflammation and PAH with vascular remodelling, with both sets of pathological findings being reversible with VIP treatment. Preliminary data suggest that absence of the VIP gene leads to activation of the calcineurin-NFAT pathway, and that VIP is probably a physiological inhibitor of this pathway. Enough evidence exists to support the views that asthma and PAH share important pathological features, probably related to NFAT activation, and that VIP may be a physiological modulator of this mechanism.