October 26, 2017AJP Lung Cellular and Molecular Physiology178 citationsOpen Access

Endothelial HIF-2α Contributes to Severe Pulmonary Hypertension by Inducing Endothelial-to-Mesenchymal Transition

HTHaiyang TangThe University of Texas at Arlington ABAleksandra BabichevaUniversity of Minnesota KMKimberly M. McDermottHoward Hughes Medical Institute

Structured PICO

Population

Mice models and normal human pulmonary artery smooth muscle cells (PASMCs) and lung vascular endothelial cells (LVECs)

Intervention

Endothelial cell (EC)-specific knockout of the HIF-2α gene (hif2a) and exposure to hypoxia

Comparator

EC-specific deletion of the HIF-1α gene (hif1a) or smooth muscle cell (SMC)-specific deletion of hif2a

Outcome

Development of hypoxia-induced pulmonary hypertension (PH)surrogate

Increased HIF-2α in lung vascular endothelial cells plays a pathogenic role in severe pulmonary hypertension by inducing endothelial-to-mesenchymal transition and vascular remodeling.

Abstract

mice. EC-specific KO of the HIF-2α gene, hif2a, prevented mice from developing hypoxia-induced PH, whereas EC-specific deletion of the HIF-1α gene, hif1a, or smooth muscle cell (SMC)-specific deletion of hif2a, negligibly affected the development of PH. Also, exposure to hypoxia for 48-72 h increased protein level of HIF-1α in normal human PASMCs and HIF-2α in normal human LVECs. These data indicate that increased HIF-2α in LVECs plays a pathogenic role in the development of severe PH by upregulating SNAI1/2, inducing EndMT, and causing obliterative pulmonary vascular lesions and vascular remodeling.

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