Mural Cell SDF1 Signaling Is Associated with the Pathogenesis of Pulmonary Arterial Hypertension

• DOI: 10.1165/rcmb.2019-0401oc
• Publication Date: 2020-02-21T22:08:35Z
• Authors: Ke Yuan; Yu Liu; Yue Zhang; Abinaya Nathan; Wen Tian; Joyce Yu; Andrew J. Sweatt; Elya A. Shamshou; David Condon; Ananya Chakraborty; Stuti Agarwal; Natasha Auer; Serena Zhang; Joseph C. Wu; Roham T. Zamanian; Mark R. Nicolls; Vinicio A. de Jes...
• Keywords: Mural cell; Pericyte; Hypoxia; Contractility

Pulmonary artery smooth muscle cells (PASMCs) and pericytes are NG2+ mural that provide structural support to pulmonary arteries capillaries. In arterial hypertension (PAH), both cell types contribute PA muscularization, but whether similar mechanisms responsible for their behavior is unknown. RNA-seq was used compare the gene profile of PASMCs from PAH healthy lungs. NG2-Cre-ER mice were generate NG2-selective reporter (NG2tdT) lineage identification tamoxifen-inducible SDF1 knockout (SDF1NG2-KO). Hierarchical clustering data demonstrated genetic highly similar. Cellular staining studies on NG2tdT in chronic hypoxia showed that, PAH, tdT+ accumulate muscularized microvessels demonstrate significant upregulation SDF1, a chemokine involved chemotaxis angiogenesis. Compared with control mice, SDF1NG2-KO had reduced muscularization lower abundance around microvessels. stimulation induced greater contractility impaired capacity establish endothelial-pericyte communications. contrast, knockdown pericyte improved associate vascular tubes coculture. upregulated associated muscularization. Targeting could help prevent and/or reverse PAH.