<oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd">
  <dc:creator>Ghimire, Kedar</dc:creator>
  <dc:creator>Li, Yao</dc:creator>
  <dc:creator>Chiba, Takuto</dc:creator>
  <dc:creator>Julovi, Sohel M.</dc:creator>
  <dc:creator>Li, Jennifer</dc:creator>
  <dc:creator>Ross, Mark A.</dc:creator>
  <dc:creator>Straub, Adam C.</dc:creator>
  <dc:creator>O’Connell, Philip J.</dc:creator>
  <dc:creator>Rüegg, Curzio</dc:creator>
  <dc:creator>Pagano, Patrick J.</dc:creator>
  <dc:creator>Isenberg, Jeffrey S.</dc:creator>
  <dc:creator>Rogers, Natasha M.</dc:creator>
  <dc:date>2020-07-15</dc:date>
  <dc:description xmlns:ns0="xml" ns0:lang="en">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.</dc:description>
  <dc:format>application/pdf</dc:format>
  <dc:identifier>https://folia.unifr.ch/global/documents/308921</dc:identifier>
  <dc:identifier>https://folia.unifr.ch/documents/308921/files/rue_cpa.pdf</dc:identifier>
  <dc:identifier>https://folia.unifr.ch/documents/308921/files/rue_cpa_sm.pdf</dc:identifier>
  <dc:language>eng</dc:language>
  <dc:relation>info:eu-repo/semantics/altIdentifier/doi/10.3390/cells9071695</dc:relation>
  <dc:rights>info:eu-repo/semantics/openAccess</dc:rights>
  <dc:rights>License undefined</dc:rights>
  <dc:source>Cells. - 2020, vol. 9, no. 7, p. 1695</dc:source>
  <dc:subject>info:eu-repo/classification/udc/57</dc:subject>
  <dc:title xmlns:ns1="xml" ns1:lang="en">CD47 promotes age-associated deterioration in angiogenesis, blood flow and glucose homeostasis</dc:title>
  <dc:type>http://purl.org/coar/resource_type/c_6501</dc:type>
</oai_dc:dc>