Pericytes contribute to pulmonary vascular remodeling via HIF2α signaling.

Autor:	Kim H; Division of Pulmonary Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA., Liu Y; Stanford Cardiovascular Institute; Department of Medicine, Stanford University, Stanford, CA, 94305, USA., Kim J; Division of Pulmonary Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA., Kim Y; Division of Pulmonary Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA., Klouda T; Division of Pulmonary Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA., Fisch S; Department of Medicine, Brigham and Women Hospital, Boston, MA, USA., Baek SH; Division of Pulmonary Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA., Liu T; Division of Pulmonary Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA., Dahlberg S; Division of Pulmonary Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA., Hu CJ; Cardiovascular Pulmonary Research Laboratories, Division of Pulmonary Sciences and Critical Care Medicine, Division of Pediatrics-Critical Care, Departments of Medicine and Pediatrics, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA., Tian W; Division of Pulmonary, Allergy and Critical Care Medicine, Dept of Medicine, Stanford University, Stanford, CA, USA., Jiang X; Division of Pulmonary, Allergy and Critical Care Medicine, Dept of Medicine, Stanford University, Stanford, CA, USA., Kosmas K; Department of Pediatric Newborn Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Christou HA; Department of Pediatric Newborn Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Korman BD; Division of Allergy/Immunology and Rheumatology, Department of Medicine, University of Rochester Medical Center, Rochester, NY, 14623, USA., Vargas SO; Division of Pathology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA., Wu JC; Stanford Cardiovascular Institute; Department of Medicine, Stanford University, Stanford, CA, 94305, USA., Stenmark KR; Cardiovascular Pulmonary Research Laboratories, Division of Pulmonary Sciences and Critical Care Medicine, Division of Pediatrics-Critical Care, Departments of Medicine and Pediatrics, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA., Perez VJ; Division of Pulmonary, Allergy and Critical Care Medicine, Dept of Medicine, Stanford University, Stanford, CA, USA., Nicolls MR; Division of Pulmonary, Allergy and Critical Care Medicine, Dept of Medicine, Stanford University, Stanford, CA, USA., Raby BA; Division of Pulmonary Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA., Yuan K; Division of Pulmonary Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. Ke.Yuan@childrens.harvard.edu.
Jazyk:	angličtina
Zdroj:	EMBO reports [EMBO Rep] 2024 Feb; Vol. 25 (2), pp. 616-645. Date of Electronic Publication: 2024 Jan 19.
DOI:	10.1038/s44319-023-00054-w
Abstrakt:	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. (© 2024. The Author(s).)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu