Postnatal pulmonary artery development from transcript to tissue

Many congenital conditions and surgical interventions perturb haemodynamics in the proximal pulmonary arteries during postnatal development, thereby altering gene expression and associated changes in vascular structure and function. Among these, pathological conditions include patent ductus arteriosus, pulmonary atresia and stenosis and hypoxemia-induced pulmonary hypertension while surgical interventions include the placement of a Blalock-Thomas-Taussig shunt and the Glenn and Fontan procedures. Despite the significant morbidity associated with these diverse conditions, little attention has been directed to understanding the natural postnatal development of pulmonary arteries from both biological and mechanical perspectives. Without such information, we cannot truly understand the phenotype of the affected pulmonary artery, which is fundamental to improving diagnosis, treatment and prognosis. In this paper, we present novel data from wild-type mice that document normal postnatal changes in select gene expression, wall composition and biomechanical properties of proximal pulmonary arteries. These findings enabled the establishment of a novel, data-informed computational model of pulmonary artery development capable of simulating outcomes in response to perturbations in pulmonary artery haemodynamics.