@article{4590d1ee4d814b9da21b262562d6b275,
title = "Neuropilin-1 maintains dimethylarginine dimethylaminohydrolase 1 expression in endothelial cells, and contributes to protection from angiotensin II-induced hypertension",
abstract = "Dimethylarginine dimethylaminohydrolases (DDAHs) are known to degrade asymmetric dimethylarginine, an endogenous inhibitor of NOS, and maintain vascular homeostasis; however, the regulatory pathways of DDAHs remain unclear. In this study, we aimed to define the role of transmembrane glycoprotein neuropilin-1 (NRP1) in the expression of DDAHs and investigate the potential roles of NRP1 in regulation of blood pressure. Short hairpin RNA-mediated knockdown of NRP1 reduced the level and mRNA stability of DDAH1 but not DDAH2 in HUVECs, whereas overexpression of NRP1 increased the mRNA stability of DDAH1. Meanwhile, mesenteric arteries and lung vascular endothelial cells of tamoxifen-inducible endothelial cell-specific NRP1 knockout mice exhibited decreased expression of DDAH1 and slightly increased expression of DDAH2. Mechanistically, the regulation of NRP1 on DDAH1 expression is mediated by a posttranscriptional mechanism involving miR-219-5p in HUVECs. Although the endothelial cell-specific NRP1 knockout mice did not exhibit any significant change in blood pressure at the basal level, they were more sensitive to low-dose angiotensin II infusion-induced increases in blood pressure. Our results show that NRP1 is required for full expression of DDAH1 in endothelial cells and that NRP1 contributes to protection from low-dose angiotensin II-induced increases in blood pressure.",
keywords = "Endothelium, High blood pressure, NO, miRNA",
author = "Ying Wang and Enfeng Wang and Yuebo Zhang and Madamsetty, {Vijay S.} and Baoan Ji and Radisky, {Derek C.} and Grande, {Joseph P.} and Sanjay Misra and Debabrata Mukhopadhyay",
note = "Funding Information: The authors thank Dr. Alex Kolodkin (Johns Hopkins University, Baltimore, MD, USA) and Dr. Ralf H. Adams (Max Planck Institute, M{\"u}nster, Germany) for the NRP1flox/flox mice and vascular endothelial–cadherin/Cre-ERT2 mice, respectively. They also thank Dr. Jordan D. Miller and Mr. Bruce E. Knudsen (Mayo Clinic) for assistance with the mouse blood pressure measurements. The authors thank the Microarray Core Facility at Mayo Clinic for their support and Brandy H. Edenfield (Mayo Clinic Jacksonville Histopathology Facility) for the kind help. The authors thank Dr. Luke H. Hoeppner (The Hormel Institute, University of Minnesota, Austin, MN, USA) for critically reviewing the manuscript, and Drs. DeLisa Fairweather and Katelyn A. Bruno (Mayo Clinic) for assistance with mouse lung endothelial cell isolation. This work was supported by U.S. National Institutes of Health (NIH) National Heart, Lung, and Blood Institute Grant HL140411, and NIH National Cancer Institute Grant CA78383-20 (both to D.M.), the Florida Department of Health Cancer Research Chair{\textquoteright}s Fund Florida Grant 3J-02 (to D.M.), and the American Heart Association Grant AHA-14POST20390029 (to Y.W.). The authors declare no conflicts of interest. Publisher Copyright: {\textcopyright} FASEB.",
year = "2019",
month = jan,
doi = "10.1096/fj.201800499R",
language = "English (US)",
volume = "33",
pages = "494--500",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "FASEB",
number = "1",
}