Increased vascular stiffness and increased pulsatile flow due to remodelling of the ECM of the pulmonary arteries is thought to play a critical role in the pathogenesis of PAH and by some to be a cause rather than a consequence of distal microvascular proliferative vasculopathy.30 Composition of the ECM is regulated by the balance between proteolytic enzymes such as the MMPs, metalloproteases (ADAMs), lysyl oxidases (LOXs) and serine elastases and their endogenous regulators, TIMPs. The gene discussed is LOX; the disease is vascular disorder.