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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.01701

Elevated neuropeptide Y in endothelial dysfunction promotes macrophage infiltration and smooth muscle foam cell formation

  • 1College of Medicine, University of Ulsan, South Korea

Abstract
Endothelial dysfunction has been linked vascular inflammation and foam cell formation but the underlying mechanisms still remain unclear. We sought to define the factors inducing inflammation and smooth muscle foam cell formation under endothelial dysfunction using endothelial nitric oxide synthase (eNOS)-deficient mice. Vascular smooth muscle cells (VSMCs) from eNOS-deficient mice displayed increased expression of macrophage-related genes and elevated lipid uptake. Neuropeptide Y (NPY) was upregulated in the aorta from the eNOS-deficient mice and promoted macrophage chemotaxis toward VSMCs while enhancing the activity of matrix metalloproteinase-3. Notably, NPY induced lipid uptake in VSMCs, facilitating smooth muscle foam cell formation, in association with enhanced expression of genes related to modified low-density lipoprotein uptake and macrophages. NPY was augmented by inflammatory pentraxin 3 (PTX3) in VSMCs. PTX3 enhanced macrophage migratory capacity through NPY/neuropeptide Y receptor axis and this effect was attenuated by pharmacological inhibition with a receptor-specific antagonist. These observations suggest that endothelial dysfunction leads to the elevation of NPY that amplifies vascular inflammation by increasing inflammatory cell chemotaxis and triggers smooth muscle foam cell formation.

Keywords: Neuropeptide Y, Pentraxin 3, smooth muscle foam cell, macrophage, Lipid, Endothelial nitric oxidase synthase

Received: 01 Oct 2018; Accepted: 08 Jul 2019.

Edited by:

Claudia Monaco, University of Oxford, United Kingdom

Reviewed by:

Sandra Donnini, University of Siena, Italy
Ljubica Perisic Matic, Karolinska Institute (KI), Sweden  

Copyright: © 2019 Chang, Choi, Shin, Kim, Park, Lee, Kim and Song. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Eun-Ju Chang, College of Medicine, University of Ulsan, Ulsan, South Korea, ejchang@amc.seoul.kr