Biology

An Age-Related Increase in CD47 Expression Impairs Vascular Function


Researchers here provide evidence to indicate that increased expression of CD47 in aged blood vessels impairs a range of functions, from maintenance of these tissues to the generation of new blood vessels. The latter point is interesting given that capillary networks become less dense with age. This is thought to impair blood flow to tissues and thus contribute to age-related loss of function. The animal evidence here suggests that inhibition of CD47 may be a viable strategy to reduce the impact of aging on the vasculature, and thus also many of the consequences of vascular aging throughout the body.

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 in arteries from aged wild-type mice and older human subjects compared to younger controls.

These perturbations were prevented in arteries from aged CD47 knockout 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 knockout 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 knockout mice were resistant to age- and diet-associated weight gain, glucose intolerance, and insulin desensitizationipedia.org/wiki/Insulin_resistance”>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.

Link: https://doi.org/10.3390/cells9071695

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