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

Ghimire, Kedar and Li, Yao and Chiba, Takuto and Julovi, Sohel M. and Li, Jennifer and Ross, Mark A. and Straub, Adam C. and O’Connell, Philip J. and Rüegg, Curzio and Pagano, Patrick J. and Isenberg, Jeffrey S. and Rogers, Natasha M. (2020) CD47 Promotes Age-Associated Deterioration in Angiogenesis, Blood Flow and Glucose Homeostasis. Cells, 9 (7). p. 1695. ISSN 2073-4409

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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.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Ghimire, Kedar
Li, Yaoyal102@pitt.eduyal102
Chiba, Takutochibat@pitt.educhibat
Julovi, Sohel M.
Li, Jennifer
Ross, Mark A.mross@pitt.edumross
Straub, Adam C.astraub@pitt.eduastraub
O’Connell, Philip J.
Rüegg, Curzio
Pagano, Patrick J.pagano@pitt.edupagano
Isenberg, Jeffrey S.
Rogers, Natasha M.
Centers: Other Centers, Institutes, Offices, or Units > Center for Biologic Imaging
Date: 15 July 2020
Date Type: Publication
Journal or Publication Title: Cells
Volume: 9
Number: 7
Publisher: MDPI AG
Page Range: p. 1695
DOI or Unique Handle: 10.3390/cells9071695
Schools and Programs: School of Medicine > Pharmacology and Chemical Biology
Refereed: Yes
Uncontrolled Keywords: aging, angiogenesis, CD47, thrombospondin-1, glucose homeostasis, metabolism
ISSN: 2073-4409
Official URL:
Funders: National Institutes of Health, National Health and Medical Research Council, Career Development Fellowship, Diabetes Australia General Grant
Article Type: Research Article
Date Deposited: 28 Jun 2021 19:12
Last Modified: 28 Jun 2021 19:12


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