Supervisor: Dr Amer Rana
Title: Mapping the effects of inflammation and hypoxia on vascular cells with reduced BMPR2 expression to model pulmonary arterial hypertension progression
Abstract: Pulmonary arterial hypertension (PAH) is a rare, debilitating and often fatal disease in which high blood pressure in the blood vessels supplying the lungs increases the strain on the right side of the heart, thus forcing it to work increasingly harder until it can no longer cope, ultimately leading to heart failure.
PAH is associated with reduced bone morphogenetic protein receptor type II (BMPR2) signalling, but it is unclear whether additional factors are required to trigger PAH. Limited human tissue is available for study and usually only from patients with end-stage disease, making it difficult to understand how PAH is established and progresses. Furthermore, BMPR2 knockout mouse models are unable to recapitulate the full repertoire of phenotypes observed in humans. We therefore require alternative human models of PAH.
We have generated induced pluripotent stem cell-derived smooth muscle cells (iPSC-SMCs), endothelial cells and cardiomyocytes from control subjects and PAH patients with BMPR2 mutations, and have shown that these cells phenotypically resemble their adult equivalents. The aim of this project is to use this novel human iPSC model of PAH to map the effects of inflammation and hypoxia on PAH establishment and progression in a way which has not been possible before.
pulmonary arterial hypertension ; pulmonary hypertension
Generation and Culture of Blood Outgrowth Endothelial Cells from Human Peripheral Blood. Ormiston ML, Toshner MR, Kiskin FN, Huang CJ, Groves E, Morrell NW, Rana AA. J Vis Exp. 2015 Dec 23;(106). doi: 10.3791/53384.