HIF2A gain-of-function mutation modulates the stiffness of smooth muscle cells and compromises vascular mechanics
Xin Yi Chan, Eugenia Volkova, Joon Eoh, Rebecca Mae Black, Lilly Fang, Rayyan Gorashi, Jihyun Song, Jing Wang, Morgan B. Elliott, Sebastian F. Barreto-Ortiz, James Chen, Brian L. Lin, Lakshmi Santhanam, Linzhao Cheng, Frank S. Lee, Josef T. Prchal, Sharon Gerecht
Abstract
-receptors both reduced HIF2-SMC stiffness. Hif2A GOF heterozygous mice displayed pulmonary hypertension, had SMCs with more disorganized stress fibers and higher stiffness in their pulmonary arterial smooth muscle cells, and had more deformable pulmonary arteries compared with wild-type mice. Our findings suggest that targeting these vascular aberrations could benefit patients with HIF2A GOF and conditions of augmented hypoxia signaling.
Topics & Concepts
MyosinVascular smooth muscleElastinEndothelin 1Hypoxia (environmental)Gene knockdownRegulatorCell biologyInternal medicineMedicineBiologyChemistryEndocrinologyReceptorPathologySmooth muscleCell cultureGeneBiochemistryGeneticsOrganic chemistryOxygenCancer, Hypoxia, and MetabolismPulmonary Hypertension Research and TreatmentsHigh Altitude and Hypoxia