Satellite Cell Expression of RAGE (Receptor for Advanced Glycation end Products) Is Important for Collateral Vessel Formation

• Type of Material: Article
• Authors: Laura Hansen, Emory University; Giji Joseph, Emory University; Alejandra Valdivia, Emory University; W. Robert Taylor, Emory University
• Language: English
• Date: 2021-11-02
• Publisher: WILEY
• Publication Version: Final Published Version
• Copyright Statement: © 2021 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1161/JAHA.120.022127
• Title of Journal or Parent Work: JOURNAL OF THE AMERICAN HEART ASSOCIATION
• Volume: 10
• Issue: 21
• Start Page: e022127
• End Page: e022127
• Grant/Funding Information: This study was supported by American Heart Association CDA 19CDA34760210 (Dr Hansen), the National Institutes of Health (NIH) F32HL124974 (Dr Hansen), and the National Center for Advancing Translational Sciences of the NIH under award UL1TR002378. In addition, this study was supported in part by the Emory Multiplexed Immunoassay Core, which is subsidized by the Emory University School of Medicine and is one of the Emory Integrated Core Facilities, with additional support provided by the National Center for Georgia Clinical & Translational Science Alliance of the NIH under award UL1TR002378. Microscopy data for this study were acquired and analyzed in the Microscopy in Medicine Core, supported by NIH grant P01 HL095070. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH (Drs Hansen and Taylor).
• Keywords: INFLAMMATION; RAGE; VASCULOPATHY; ANGIOGENESIS; ACTIVATION; MECHANISM; NITRIC-OXIDE; Cardiovascular System & Cardiology; GROWTH; collateral vessels; ENDOTHELIAL-CELLS; Cardiac & Cardiovascular Systems; VASCULAR DYSFUNCTION; Life Sciences & Biomedicine; satellite cells; Science & Technology; PATHWAYS
• Research Categories: Health Sciences, Medicine and Surgery; Engineering, Biomedical

Abstract

BACKGROUND: The growth and remodeling of vascular networks is an important component of the prognosis for patients with peripheral artery disease. One protein that has been previously implicated to play a role in this process is RAGE (receptor for advanced glycation end products). This study sought to determine the cellular source of RAGE in the ischemic hind limb and the role of RAGE signaling in this cell type. METHODS AND RESULTS: Using a hind limb ischemia model of vascular growth, this study found skeletal muscle satellite cells to be a novel major cellular source of RAGE in ischemic tissue by both staining and cellular sorting. Although wild-type satellite cells increased tumor necrosis factor-α and monocyte chemoattractant protein-1 production in response to ischemia in vivo and a RAGE ligand in vitro, satellite cells from RAGE knockout mice lacked the increase in cytokine production both in vivo in response to ischemia and in vitro after stimuli with the RAGE ligand high-mobility group box 1. Furthermore, encapsulated wild-type satellite cells improved perfusion after hind limb ischemia surgery by both perfusion staining and vessel quantification, but RAGE knockout satellite cells provided no improvement over empty capsules. CONCLUSIONS: Thus, RAGE expression and signaling in satellite cells is crucial for their response to stimuli and angiogenic and arteriogenic functions.