The Effects of SRT1720 Treatment on Endothelial Cells Derived from the Lung and Bone Marrow of Young and Aged, Male and Female Mice

Int J Mol Sci. 2021 Oct 14;22(20):11097. doi: 10.3390/ijms222011097.

Abstract

Angiogenesis is critical for successful fracture healing. Age-related alterations in endothelial cells (ECs) may cause impaired bone healing. Therefore, examining therapeutic treatments to improve angiogenesis in aging may enhance bone healing. Sirtuin 1 (SIRT1) is highly expressed in ECs and its activation is known to counteract aging. Here, we examined the effects of SRT1720 treatment (SIRT1 activator) on the growth and function of bone marrow and lung ECs (BMECs and LECs, respectively), derived from young (3-4 month) and old (20-24 month) mice. While aging did not alter EC proliferation, treatment with SRT1720 significantly increased proliferation of all LECs. However, SRT1720 only increased proliferation of old female BMECs. Vessel-like tube assays showed similar vessel-like structures between young and old LECs and BMECs from both male and female mice. SRT1720 significantly improved vessel-like structures in all LECs. No age, sex, or treatment differences were found in migration related parameters of LECs. In males, old BMECs had greater migration rates than young BMECs, whereas in females, old BMECs had lower migration rates than young BMECs. Collectively, our data suggest that treatment with SRT1720 appears to enhance the angiogenic potential of LECs irrespective of age or sex. However, its role in BMECs is sex- and age-dependent.

Keywords: Sirtuin 1; aging; angiogenesis; bone; endothelial cells; lungs.

MeSH terms

  • Aging / physiology*
  • Angiopoietin-1 / genetics
  • Animals
  • Bone Marrow Cells / drug effects*
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Endothelial Cells / drug effects
  • Female
  • Gene Expression Regulation / drug effects
  • Heterocyclic Compounds, 4 or More Rings / pharmacology*
  • Lung / cytology*
  • Male
  • Mice, Inbred C57BL
  • Neovascularization, Physiologic / drug effects*
  • Neovascularization, Physiologic / physiology
  • Sirtuin 1 / genetics
  • Vascular Endothelial Growth Factor Receptor-1 / genetics

Substances

  • Angiopoietin-1
  • Angpt1 protein, mouse
  • Heterocyclic Compounds, 4 or More Rings
  • SRT1720
  • Flt1 protein, mouse
  • Vascular Endothelial Growth Factor Receptor-1
  • Sirt1 protein, mouse
  • Sirtuin 1