Sphingosine 1-phosphate activation of ERM contributes to vascular calcificationCitation formats

  • External authors:
  • Thomas Morris
  • Christopher J Clarke
  • Yusuf A Hannun
  • Vasken Ohanian

Standard

Sphingosine 1-phosphate activation of ERM contributes to vascular calcification. / Morris, Thomas; Borland, Samantha; Clarke, Christopher J; Wilson, Claire; Hannun, Yusuf A; Ohanian, Vasken; Canfield, Ann; Ohanian, Jacqueline.

In: Journal of Lipid Research, Vol. 59, DOI https://doi.org/10.1194/jlr.M079731, 01.2018, p. 69-78.

Research output: Contribution to journalArticle

Harvard

Morris, T, Borland, S, Clarke, CJ, Wilson, C, Hannun, YA, Ohanian, V, Canfield, A & Ohanian, J 2018, 'Sphingosine 1-phosphate activation of ERM contributes to vascular calcification', Journal of Lipid Research, vol. 59, DOI https://doi.org/10.1194/jlr.M079731, pp. 69-78. https://doi.org/10.1194/jlr.M079731

APA

Morris, T., Borland, S., Clarke, C. J., Wilson, C., Hannun, Y. A., Ohanian, V., Canfield, A., & Ohanian, J. (2018). Sphingosine 1-phosphate activation of ERM contributes to vascular calcification. Journal of Lipid Research, 59, 69-78. [DOI https://doi.org/10.1194/jlr.M079731]. https://doi.org/10.1194/jlr.M079731

Vancouver

Morris T, Borland S, Clarke CJ, Wilson C, Hannun YA, Ohanian V et al. Sphingosine 1-phosphate activation of ERM contributes to vascular calcification. Journal of Lipid Research. 2018 Jan;59:69-78. DOI https://doi.org/10.1194/jlr.M079731. https://doi.org/10.1194/jlr.M079731

Author

Morris, Thomas ; Borland, Samantha ; Clarke, Christopher J ; Wilson, Claire ; Hannun, Yusuf A ; Ohanian, Vasken ; Canfield, Ann ; Ohanian, Jacqueline. / Sphingosine 1-phosphate activation of ERM contributes to vascular calcification. In: Journal of Lipid Research. 2018 ; Vol. 59. pp. 69-78.

Bibtex

@article{05065be85e0349b4a9f595d5a07500b3,
title = "Sphingosine 1-phosphate activation of ERM contributes to vascular calcification",
abstract = "Vascular calcification is the deposition of mineral in the artery wall by vascular smooth muscle cells (VSMCs) in response to pathological stimuli. The process is similar to bone formation and is an independent risk factor for cardiovascular disease. Given that ceramide and sphingosine 1-phosphate (S1P) are involved in cardiovascular pathophysiology and biomineralization, their role in VSMC matrix mineralization was investigated. During phosphate-induced VSMC mineralization, endogenous S1P levels increased accompanied by increased sphingosine kinase (SK) activity and increased mRNA expression of SK1 and SK2. Consistent with this, mineralization was increased by exogenous S1P, but decreased by C2-ceramide. Mechanistically, exogenous S1P stimulated ezrin-radixin-moesin (ERM) phosphorylation in VSMCs and ERM phosphorylation was increased concomitantly with endogenous S1P during mineralization. Moreover, inhibition of acid sphingomyelinase and ceramidase with desipramine prevented increased S1P levels, ERM activation, and mineralization. Finally, pharmacological inhibition of ERM phosphorylation with NSC663894 decreased mineralization induced by phosphate and exogenous S1P. Although further studies will be needed to verify these findings in vivo, this study defines a novel role for the SK-S1P-ERM pathways in phosphate-induced VSMC matrix mineralization and shows that blocking these pathways with pharmacological inhibitors reduces mineralization. These results may inform new therapeutic approaches to inhibit or delay vascular calcification.",
author = "Thomas Morris and Samantha Borland and Clarke, {Christopher J} and Claire Wilson and Hannun, {Yusuf A} and Vasken Ohanian and Ann Canfield and Jacqueline Ohanian",
year = "2018",
month = jan
doi = "10.1194/jlr.M079731",
language = "English",
volume = "59",
pages = "69--78",
journal = "Journal of Lipid Research",
issn = "0022-2275",
publisher = "American Society for Biochemistry and Molecular Biology",

}

RIS

TY - JOUR

T1 - Sphingosine 1-phosphate activation of ERM contributes to vascular calcification

AU - Morris, Thomas

AU - Borland, Samantha

AU - Clarke, Christopher J

AU - Wilson, Claire

AU - Hannun, Yusuf A

AU - Ohanian, Vasken

AU - Canfield, Ann

AU - Ohanian, Jacqueline

PY - 2018/1

Y1 - 2018/1

N2 - Vascular calcification is the deposition of mineral in the artery wall by vascular smooth muscle cells (VSMCs) in response to pathological stimuli. The process is similar to bone formation and is an independent risk factor for cardiovascular disease. Given that ceramide and sphingosine 1-phosphate (S1P) are involved in cardiovascular pathophysiology and biomineralization, their role in VSMC matrix mineralization was investigated. During phosphate-induced VSMC mineralization, endogenous S1P levels increased accompanied by increased sphingosine kinase (SK) activity and increased mRNA expression of SK1 and SK2. Consistent with this, mineralization was increased by exogenous S1P, but decreased by C2-ceramide. Mechanistically, exogenous S1P stimulated ezrin-radixin-moesin (ERM) phosphorylation in VSMCs and ERM phosphorylation was increased concomitantly with endogenous S1P during mineralization. Moreover, inhibition of acid sphingomyelinase and ceramidase with desipramine prevented increased S1P levels, ERM activation, and mineralization. Finally, pharmacological inhibition of ERM phosphorylation with NSC663894 decreased mineralization induced by phosphate and exogenous S1P. Although further studies will be needed to verify these findings in vivo, this study defines a novel role for the SK-S1P-ERM pathways in phosphate-induced VSMC matrix mineralization and shows that blocking these pathways with pharmacological inhibitors reduces mineralization. These results may inform new therapeutic approaches to inhibit or delay vascular calcification.

AB - Vascular calcification is the deposition of mineral in the artery wall by vascular smooth muscle cells (VSMCs) in response to pathological stimuli. The process is similar to bone formation and is an independent risk factor for cardiovascular disease. Given that ceramide and sphingosine 1-phosphate (S1P) are involved in cardiovascular pathophysiology and biomineralization, their role in VSMC matrix mineralization was investigated. During phosphate-induced VSMC mineralization, endogenous S1P levels increased accompanied by increased sphingosine kinase (SK) activity and increased mRNA expression of SK1 and SK2. Consistent with this, mineralization was increased by exogenous S1P, but decreased by C2-ceramide. Mechanistically, exogenous S1P stimulated ezrin-radixin-moesin (ERM) phosphorylation in VSMCs and ERM phosphorylation was increased concomitantly with endogenous S1P during mineralization. Moreover, inhibition of acid sphingomyelinase and ceramidase with desipramine prevented increased S1P levels, ERM activation, and mineralization. Finally, pharmacological inhibition of ERM phosphorylation with NSC663894 decreased mineralization induced by phosphate and exogenous S1P. Although further studies will be needed to verify these findings in vivo, this study defines a novel role for the SK-S1P-ERM pathways in phosphate-induced VSMC matrix mineralization and shows that blocking these pathways with pharmacological inhibitors reduces mineralization. These results may inform new therapeutic approaches to inhibit or delay vascular calcification.

U2 - 10.1194/jlr.M079731

DO - 10.1194/jlr.M079731

M3 - Article

VL - 59

SP - 69

EP - 78

JO - Journal of Lipid Research

JF - Journal of Lipid Research

SN - 0022-2275

M1 - DOI https://doi.org/10.1194/jlr.M079731

ER -