Endothelial Autocrine Signaling through CXCL12/CXCR4/FoxM1 Axis Contributes to Severe Pulmonary Arterial Hypertension

• DOI: 10.20944/preprints202102.0332.v3
• Publication Date: 2021-03-22T15:12:03Z
• Authors: Dan Yi; Bin Liu; Ting Wang; Qi Liao; Maggie M. Zhu; You-Yang Zhao; Zhiyu Dai
• Keywords: FOXM1

Endothelial autocrine signaling is essential to maintain vascular hemostasis. There limited in-formation about the role of endothelial in regulating severe pulmonary vas-cular remodeling during onset arterial hypertension (PAH). In this study, we employed first PAH mouse model, Egln1Tie2Cre (Tie2Cre-mediated disruption Egln1) mice, identify novel mediating cells (PVECs) hyperproliferation and pathogenesis PAH. PVECs isolated from lung expressed upregulation many growth factors or angiocrine such as CXCL12, exhib-ited hyperproliferative phenotype coincident with proliferation specific tran-scriptional factor FoxM1. Treatment CXCL12 on increased FoxM1 expression, which was blocked by receptor CXCR4 antagonist AMD3100 culture human PVECs. Endo-thelial deletion Cxcl12 (Egln1/Cxcl12Tie2 Cre) treatment mice downregulated expression vivo. We then generated characterized a model (Egln1/Foxm1Tie2Cre), found that reduced right ventricular systolic pressure. Together, our study identified mechanism sig-naling