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

Cells
Kedar GhimireNatasha M Rogers

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 deteriorati...Continue Reading

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Citations

Apr 16, 2021·Frontiers in Endocrinology·Linda S Gutierrez, Jovita Gutierrez
Apr 21, 2021·ACS Applied Materials & Interfaces·Chengpan LiWeiping Ding
May 1, 2021·International Journal of Molecular Sciences·Atharva KaleKedar Ghimire
Jun 10, 2021·American Journal of Physiology. Cell Physiology·David D Roberts, Jeffrey S Isenberg

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Methods Mentioned

BETA
PCR
protein assay
electrophoresis
Assay
scraping

Software Mentioned

Angiogenesis Analyzer Program for ImageJ
ImageJ
Nikon Elements
TScratch

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