Mycophenolic acid induces senescence of vascular precursor cells

Ellen Go, Stefan P. Tarnawsky, W. Chris Shelley, Kimihiko Banno, Yang Lin, Chang Hyun Gil, Emily K. Blue, Laura Haneline, Kathleen M. O'Neil, Mervin Yoder

Research output: Contribution to journalArticle

Abstract

Objective: Endothelial dysfunction is central to the pathogenesis of many rheumatic diseases, typified by vascular inflammation and damage. Immunosuppressive drugs induce disease remission and lead to improved patient survival. However, there remains a higher incidence of cardiovascular disease in these patients even after adequate disease control. The purpose of this study was to determine the effect of mycophenolic acid (MPA), a commonly used immunosuppressive drug in rheumatology, on blood vessel or circulating endothelial colony forming cell number and function. Methods: We tested whether mycophenolic acid exerts an inhibitory effect on proliferation, clonogenic potential and vasculogenic function of endothelial colony forming cell. We also studied potential mechanisms involved in the observed effects. Results: Treatment with MPA decreased endothelial colony forming cell proliferation, clonogenic potential and vasculogenic function in a dose-dependent fashion. MPA increased senescence-associated β-galactosidase expression, p21 gene expression and p53 phosphorylation, indicative of activation of cellular senescence. Exogenous guanosine supplementation rescued diminished endothelial colony forming cell proliferation and indices of senescence, consistent with the known mechanism of action of MPA. Conclusion: Our findings show that clinically relevant doses of MPA have potent anti-angiogenic and pro-senescent effects on vascular precursor cells in vitro, thus indicating that treatment with MPA can potentially affect vascular repair and regeneration. This warrants further studies in vivo to determine how MPA therapy contributes to vascular dysfunction and increased cardiovascular disease seen in patients with inflammatory rheumatic disease.

Original languageEnglish (US)
Article numbere0193749
JournalPLoS One
Volume13
Issue number3
DOIs
StatePublished - Mar 1 2018

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Mycophenolic Acid
blood vessels
Blood Vessels
acids
cells
immunosuppressive agents
Cell proliferation
Immunosuppressive Agents
Rheumatic Diseases
cardiovascular diseases
cell proliferation
Cardiovascular Diseases
Cell Proliferation
Galactosidases
Disease control
galactosidases
drugs
guanosine
Phosphorylation
Guanosine

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Go, E., Tarnawsky, S. P., Shelley, W. C., Banno, K., Lin, Y., Gil, C. H., ... Yoder, M. (2018). Mycophenolic acid induces senescence of vascular precursor cells. PLoS One, 13(3), [e0193749]. https://doi.org/10.1371/journal.pone.0193749

Mycophenolic acid induces senescence of vascular precursor cells. / Go, Ellen; Tarnawsky, Stefan P.; Shelley, W. Chris; Banno, Kimihiko; Lin, Yang; Gil, Chang Hyun; Blue, Emily K.; Haneline, Laura; O'Neil, Kathleen M.; Yoder, Mervin.

In: PLoS One, Vol. 13, No. 3, e0193749, 01.03.2018.

Research output: Contribution to journalArticle

Go, E, Tarnawsky, SP, Shelley, WC, Banno, K, Lin, Y, Gil, CH, Blue, EK, Haneline, L, O'Neil, KM & Yoder, M 2018, 'Mycophenolic acid induces senescence of vascular precursor cells', PLoS One, vol. 13, no. 3, e0193749. https://doi.org/10.1371/journal.pone.0193749
Go E, Tarnawsky SP, Shelley WC, Banno K, Lin Y, Gil CH et al. Mycophenolic acid induces senescence of vascular precursor cells. PLoS One. 2018 Mar 1;13(3). e0193749. https://doi.org/10.1371/journal.pone.0193749
Go, Ellen ; Tarnawsky, Stefan P. ; Shelley, W. Chris ; Banno, Kimihiko ; Lin, Yang ; Gil, Chang Hyun ; Blue, Emily K. ; Haneline, Laura ; O'Neil, Kathleen M. ; Yoder, Mervin. / Mycophenolic acid induces senescence of vascular precursor cells. In: PLoS One. 2018 ; Vol. 13, No. 3.
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