Next Article in Journal
What Have In Vitro Co-Culture Models Taught Us about the Contribution of Epithelial-Mesenchymal Interactions to Airway Inflammation and Remodeling in Asthma?
Next Article in Special Issue
Molecular and Mechanobiological Pathways Related to the Physiopathology of FPLD2
Previous Article in Journal
Role of Mitochondria in Cancer Stem Cell Resistance
Previous Article in Special Issue
miR-7 Regulates GLP-1-Mediated Insulin Release by Targeting β-Arrestin 1
Open AccessArticle

CD47 Promotes Age-Associated Deterioration in Angiogenesis, Blood Flow and Glucose Homeostasis

1
Centre for Transplant and Renal Research, Westmead Institute for Medical Research, University of Sydney, 176 Hawkesbury Rd, Sydney 2145, NSW, Australia
2
Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, BST Starzl Tower, 200 Lothrop Street, Pittsburgh, PA 15261, USA
3
Department of Pharmacology & Chemical Biology, University of Pittsburgh, BST Starzl Tower, 200 Lothrop Street, Pittsburgh, PA 15261, USA
4
Center for Biologic Imaging, University of Pittsburgh School of Medicine, BST, 200 Lothrop Street, Pittsburgh, PA 15261, USA
5
Department of Oncology, Microbiology and Immunology, Faculty of Sciences and Medicine, University of Fribourg, Chemin du Musée 18, PER 17, 1700 Fribourg, Switzerland
6
Department of Medicine, University of Pittsburgh, BST Starzl Tower, 200 Lothrop Street, Pittsburgh, PA 15261, USA
*
Authors to whom correspondence should be addressed.
Cells 2020, 9(7), 1695; https://doi.org/10.3390/cells9071695
Received: 21 May 2020 / Revised: 7 July 2020 / Accepted: 11 July 2020 / Published: 15 July 2020
(This article belongs to the Special Issue Molecular Mechanisms in Metabolic Disease)
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. View Full-Text
Keywords: aging; angiogenesis; CD47; thrombospondin-1; glucose homeostasis; metabolism; self-renewal; endothelial cells; blood flow aging; angiogenesis; CD47; thrombospondin-1; glucose homeostasis; metabolism; self-renewal; endothelial cells; blood flow
Show Figures

Graphical abstract

MDPI and ACS Style

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. CD47 Promotes Age-Associated Deterioration in Angiogenesis, Blood Flow and Glucose Homeostasis. Cells 2020, 9, 1695.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop