Pulmonary Vascular Platform Models the Effects of Flow and Pressure on Endothelial Dysfunction in BMPR2 Associated Pulmonary Arterial Hypertension

International Journal of Molecular Sciences
Reid W D'AmicoJames D West

Abstract

Endothelial dysfunction is a known consequence of bone morphogenetic protein type II receptor (BMPR2) mutations seen in pulmonary arterial hypertension (PAH). However, standard 2D cell culture models fail to mimic the mechanical environment seen in the pulmonary vasculature. Hydrogels have emerged as promising platforms for 3D disease modeling due to their tunable physical and biochemical properties. In order to recreate the mechanical stimuli seen in the pulmonary vasculature, we have created a novel 3D hydrogel-based pulmonary vasculature model ("artificial arteriole") that reproduces the pulsatile flow rates and pressures seen in the human lung. Using this platform, we studied both Bmpr2R899X and WT endothelial cells to better understand how the addition of oscillatory flow and physiological pressure influenced gene expression, cell morphology, and cell permeability. The addition of oscillatory flow and pressure resulted in several gene expression changes in both WT and Bmpr2R899X cells. However, for many pathways with relevance to PAH etiology, Bmpr2R899X cells responded differently when compared to the WT cells. Bmpr2R899X cells were also found not to elongate in the direction of flow, and instead remained stagnant in morp...Continue Reading

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Citations

Jun 4, 2019·Journal of Cardiovascular Translational Research·Ampadu O JacksonKai Yin
Dec 19, 2019·International Journal of Molecular Sciences·Jarrod W BarnesRaed A Dweik
Mar 5, 2020·Cellular and Molecular Life Sciences : CMLS·Jialong YanLinxi Chen

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BETA
GTPase
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transgenic

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Matlab
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TopHat
Bowtie2
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