Pericytes contribute to pulmonary vascular remodeling via HIF2a signaling [lung]
Vascular remodeling is the process of structural alteration and cell rearrangement of blood vessels in response to injury and is the cause of many of the world's most afflicted cardiovascular conditions, including pulmonary arterial hypertension(PAH). Many studies have focused on the effects of vascular endothelial cells and smooth muscle cells(SMCs) during vascular remodeling, but pericytes, an indispensable cell population residing largely in capillaries, are ignored in this maladaptive process. Here we report that hypoxia-inducible factor 2a(HIF2a) expression is increased in human PAH patient lung tissues and HIF2a overexpressed pericytes result in greater contractility and an impaired endothelial-pericyte interaction. Using single-cell RNAseq and hypoxia-induced pulmonary hypertension(PH) models, we show HIF2a as a major molecular regulator for pericytes' transformation into SMC-like cells. HIF2a overexpression in pericyte-selective mice exacerbate PH and right ventricular hypertrophy. Temporal cellular lineage tracing shows that HIF2a overexpressing reporter NG2+ cells (pericyte-selective) relocate from capillaries to arterioles and co-express SMA. This novel insight into the potential role of NG2+ pericytes in pulmonary vascular remodeling via HIF2a signaling suggests a potential drug target for PH. Overall design: single-cell RNA-seq analysis on mouse lungs after three weeks of hypoxia or without hypoxia