Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/126892
Citations
Scopus Web of Science® Altmetric
?
?
Type: Journal article
Title: CD47 promotes age-associated deterioration in angiogenesis, blood flow and glucose homeostasis
Author: Ghimire, K.
Li, Y.
Chiba, T.
Julovi, S.M.
Li, J.
Ross, M.A.
Straub, A.C.
O'Connell, P.J.
Rüegg, C.
Pagano, P.J.
Isenberg, J.S.
Rogers, N.M.
Citation: Cells, 2020; 9(7):E1695-
Publisher: MDPI
Issue Date: 2020
ISSN: 2073-4409
2073-4409
Statement of
Responsibility: 
Kedar Ghimire, Yao Li, Takuto Chiba, Sohel M. Julovi, Jennifer Li, Mark A. Ross ... Natasha M. Rogers ... et al.
Abstract: The aged population is currently at its highest level in human history and is expected to increase further in the coming years. In humans, aging is accompanied by impaired angiogenesis, diminished blood flow and altered metabolism, among others. A cellular mechanism that impinges upon these manifestations of aging can be a suitable target for therapeutic intervention. Here we identify cell surface receptor CD47 as a novel age-sensitive driver of vascular and metabolic dysfunction. With the natural aging process, CD47 and its ligand thrombospondin-1 were increased, concurrent with a reduction of self-renewal transcription factors OCT4, SOX2, KLF4 and cMYC (OSKM) in arteries from aged wild-type mice and older human subjects compared to younger controls. These perturbations were prevented in arteries from aged CD47-null mice. Arterial endothelial cells isolated from aged wild-type mice displayed cellular exhaustion with decreased proliferation, migration and tube formation compared to cells from aged CD47-null mice. CD47 suppressed ex vivo sprouting, in vivo angiogenesis and skeletal muscle blood flow in aged wild-type mice. Treatment of arteries from older humans with a CD47 blocking antibody mitigated the age-related deterioration in angiogenesis. Finally, aged CD47-null mice were resistant to age- and diet-associated weight gain, glucose intolerance and insulin desensitization. These results indicate that the CD47-mediated signaling maladapts during aging to broadly impair endothelial self-renewal, angiogenesis, perfusion and glucose homeostasis. Our findings provide a strong rationale for therapeutically targeting CD47 to minimize these dysfunctions during aging.
Keywords: Aging; angiogenesis; CD47; thrombospondin-1; glucose homeostasis; metabolism; self-renewal; endothelial cells; blood flow
Rights: © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
DOI: 10.3390/cells9071695
Grant ID: http://purl.org/au-research/grants/nhmrc/1156977
http://purl.org/au-research/grants/nhmrc/GNT1138372
Appears in Collections:Aurora harvest 4
Medicine publications

Files in This Item:
There are no files associated with this item.


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.