Seeking the right targets: gene therapy advances in pulmonary arterial hypertension.

P ulmonary arterial hypertension (PAH) is a grave vascular disorder characterised by the obstruction and occlusion of the small pulmonary arteries, primarily through the abnormal proliferation of the endothelial and smooth muscle layers. A clinical diagnosis of pulmonary hypertension (PH) is made when the mean pulmonary arterial pressure (P̄pa) is o25 mmHg at rest. An additional criterion to differentiate PAH from other forms of PH requires that pulmonary arterial wedge pressure be o15 mmHg [1, 2]. The disease is typically fatal due to right heart failure as a result of the pathological increases in pulmonary vascular resistance. While the majority of the patient population develop spontaneous or idiopathic PAH and PAH associated with other disorders, for example, HIV infection, connective tissue disease or exposure to risk factors such as appetite suppressants containing dex/fenfluramine (associated PAH), some 10% display familial transmission. In families, PAH is an autosomal dominant trait with a sex bias favouring females and penetrance as low as 20%, features that suggest that, while a Mendelian condition, PAH displays features of complex disease [1, 2].