A MICROFLUIDIC CHIP FOR PULMONARY ARTERIAL HYPERTENSION

Abstract Pulmonary arterial hypertension (PAH) is an unmet clinical need. The lack of a disease model representative of the human condition is a key obstacle to the development of new treatments. Here we present a model of PAH, based on a biomimetic pulmonary artery (PA)-on-a-chip, that permits the study of the molecular and functional changes in human pulmonary vascular endothelial and smooth muscle cells in response to triggers of the disease and their response to drugs. We combine natural or induced BMPR2 dysfunction with hypoxia in vascular endothelial cells to trigger smooth muscle activation and proliferation and relate accompanying transcriptomic changes in affected cells to functional effects. Changes in gene expression consistent with observations made in genomic and biochemical studies of the human disease enable insights into underlying disease pathways and mechanisms of drug response. The model offers a novel, promising and more easily accessible approach for researchers to study pulmonary vascular remodelling and advance drug development in PAH.