High glucose downregulates endothelial progenitor cell number via SIRT1

Maria Luisa Balestrieri, Monica Rienzo, Francesca Felice, Raffaele Rossiello, Vincenzo Grimaldi, Lara Milone, Amelia Casamassimi, Luigi Servillo, Bartolomeo Farzati, Alfonso Giovane, Claudio Napoli

Research output: Contribution to journalArticle

Abstract

Increasing evidence indicates that mammalian SIRT1 mediates calorie restriction and influences lifespan regulating a number of biological molecules such as FoxO1. SIRT1 controls the angiogenic activity of endothelial cells via deacetylation of FoxO1. Endothelial dysfunction and reduced new blood vessel growth in diabetes involve a decreased bioactivity of endothelial progenitor cells (EPCs) via repression of FoxO1 transcriptional activity. The relative contribution of SIRT1 with respect to the direct effects of high glucose on EPC number is poorly understood. We report that treatment of EPCs with high glucose for 3 days determined a consistent downregulation of EPC positive to DiLDL/lectin staining and, interestingly, this was associated with reduced SIRT1 expression levels and enzyme activity, and increased acetyl-FoxO1 expression levels. Moreover, EPCs responded to high glucose with major changes in the expression levels of cell metabolism-, cell cycle-, and oxidative stress-related genes or proteins. Proteomic analysis shows increased expression of nicotinamide phosphorybosyl transferase and mitochondrial superoxide dismutase whereas a glucose-related heat shock protein is reduced. These findings show that SIRT1 is a critical modulator of EPCs dysfunction during alteration of glucose metabolism.

Original languageEnglish
Pages (from-to)936-945
Number of pages10
JournalBiochimica et Biophysica Acta - Proteins and Proteomics
Volume1784
Issue number6
DOIs
Publication statusPublished - Jun 2008

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Keywords

  • Endothelial progenitor cells
  • Glucose
  • SIRT1

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Genetics

Cite this

Balestrieri, M. L., Rienzo, M., Felice, F., Rossiello, R., Grimaldi, V., Milone, L., Casamassimi, A., Servillo, L., Farzati, B., Giovane, A., & Napoli, C. (2008). High glucose downregulates endothelial progenitor cell number via SIRT1. Biochimica et Biophysica Acta - Proteins and Proteomics, 1784(6), 936-945. https://doi.org/10.1016/j.bbapap.2008.03.004