Pericytes contribute to pulmonary vascular remodeling via HIF2α signaling.
Hyunbum KimYu LiuJiwon KimYunhye KimTimothy KloudaSudeshna FischSeung Han BaekTiffany LiuSuzanne DahlbergCheng-Jun HuWen TianXinguo JiangKosmas KosmasHelen A ChristouBenjamin D KormanSara O VargasJoseph C WuKurt R StenmarkVinicio A de Jesus PerezMark Robert NicollsBenjamin A RabyKe YuanPublished in: EMBO reports (2024)
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 2α (HIF2α) expression is increased in the lung tissues of PAH patients, and HIF2α 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 that HIF2α is a major molecular regulator for the transformation of pericytes into SMC-like cells. Pericyte-selective HIF2α overexpression in mice exacerbates PH and right ventricular hypertrophy. Temporal cellular lineage tracing shows that HIF2α overexpressing reporter NG2+ cells (pericyte-selective) relocate from capillaries to arterioles and co-express SMA. This novel insight into the crucial role of NG2+ pericytes in pulmonary vascular remodeling via HIF2α signaling suggests a potential drug target for PH.
Keyphrases
- endothelial cells
- pulmonary hypertension
- single cell
- pulmonary arterial hypertension
- blood brain barrier
- pulmonary artery
- rna seq
- end stage renal disease
- high glucose
- gene expression
- chronic kidney disease
- transcription factor
- stem cells
- oxidative stress
- prognostic factors
- newly diagnosed
- ejection fraction
- crispr cas
- poor prognosis
- cell proliferation
- climate change
- bone marrow
- insulin resistance
- skeletal muscle
- adverse drug