Hypertension Is Associated with Marked Alterations in Sphingolipid Biology: A Potential Role for Ceramide

Leon J. A. Spijkers; Rob F. P. van den Akker; Ben J. A. Janssen; Jacques J. Debets; Jo G. R. De Mey; Erik S. G. Stroes; Bert-Jan H. van den Born; Dayanjan S. Wijesinghe; Charles E. Chalfant; Luke MacAleese; Gert B. Eijkel; Ron M. A. Heeren; Astrid E. Alewijnse; Stephan L. M. Peters

doi:10.1371/journal.pone.0021817

Hypertension Is Associated with Marked Alterations in Sphingolipid Biology: A Potential Role for Ceramide

Leon J. A. Spijkers^*
, Rob F. P. van den Akker
, Ben J. A. Janssen
, Jacques J. Debets
, Jo G. R. De Mey
, Erik S. G. Stroes
, Bert-Jan H. van den Born
, Dayanjan S. Wijesinghe
, Charles E. Chalfant
, Luke MacAleese
, Gert B. Eijkel
, Ron M. A. Heeren
, Astrid E. Alewijnse
, Stephan L. M. Peters

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Background: Hypertension is, amongst others, characterized by endothelial dysfunction and vascular remodeling. As sphingolipids have been implicated in both the regulation of vascular contractility and growth, we investigated whether sphingolipid biology is altered in hypertension and whether this is reflected in altered vascular function. Methods and Findings: In isolated carotid arteries from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats, shifting the ceramide/S1P ratio towards ceramide dominance by administration of a sphingosine kinase inhibitor (dimethylsphingosine) or exogenous application of sphingomyelinase, induced marked endothelium-dependent contractions in SHR vessels (DMS: 1.4 +/- 0.4 and SMase: 2.1 +/- 0.1 mN/mm; n = 10), that were virtually absent in WKY vessels (DMS: 0.0 +/- 0.0 and SMase: 0.6 +/- 0.1 mN/mm; n = 9, p

Original language	English
Pages (from-to)	9
Journal	PLOS ONE
Volume	6
Issue number	7
DOIs	https://doi.org/10.1371/journal.pone.0021817
Publication status	Published - 19 Jul 2011

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Spijkers, L. J. A., van den Akker, R. F. P., Janssen, B. J. A., Debets, J. J., De Mey, J. G. R., Stroes, E. S. G., van den Born, B.-J. H., Wijesinghe, D. S., Chalfant, C. E., MacAleese, L., Eijkel, G. B., Heeren, R. M. A., Alewijnse, A. E., & Peters, S. L. M. (2011). Hypertension Is Associated with Marked Alterations in Sphingolipid Biology: A Potential Role for Ceramide. PLOS ONE, 6(7), 9. https://doi.org/10.1371/journal.pone.0021817

@article{d6adc9fae0ae44f4a995551fe1bf8c3c,

title = "Hypertension Is Associated with Marked Alterations in Sphingolipid Biology: A Potential Role for Ceramide",

abstract = "Background: Hypertension is, amongst others, characterized by endothelial dysfunction and vascular remodeling. As sphingolipids have been implicated in both the regulation of vascular contractility and growth, we investigated whether sphingolipid biology is altered in hypertension and whether this is reflected in altered vascular function. Methods and Findings: In isolated carotid arteries from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats, shifting the ceramide/S1P ratio towards ceramide dominance by administration of a sphingosine kinase inhibitor (dimethylsphingosine) or exogenous application of sphingomyelinase, induced marked endothelium-dependent contractions in SHR vessels (DMS: 1.4 +/- 0.4 and SMase: 2.1 +/- 0.1 mN/mm; n = 10), that were virtually absent in WKY vessels (DMS: 0.0 +/- 0.0 and SMase: 0.6 +/- 0.1 mN/mm; n = 9, p",

author = "Spijkers, \{Leon J. A.\} and \{van den Akker\}, \{Rob F. P.\} and Janssen, \{Ben J. A.\} and Debets, \{Jacques J.\} and \{De Mey\}, \{Jo G. R.\} and Stroes, \{Erik S. G.\} and \{van den Born\}, \{Bert-Jan H.\} and Wijesinghe, \{Dayanjan S.\} and Chalfant, \{Charles E.\} and Luke MacAleese and Eijkel, \{Gert B.\} and Heeren, \{Ron M. A.\} and Alewijnse, \{Astrid E.\} and Peters, \{Stephan L. M.\}",

year = "2011",

month = jul,

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doi = "10.1371/journal.pone.0021817",

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journal = "PLOS ONE",

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Spijkers, LJA, van den Akker, RFP, Janssen, BJA , Debets, JJ, De Mey, JGR, Stroes, ESG, van den Born, B-JH, Wijesinghe, DS, Chalfant, CE, MacAleese, L, Eijkel, GB, Heeren, RMA, Alewijnse, AE & Peters, SLM 2011, 'Hypertension Is Associated with Marked Alterations in Sphingolipid Biology: A Potential Role for Ceramide', PLOS ONE, vol. 6, no. 7, pp. 9. https://doi.org/10.1371/journal.pone.0021817

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T1 - Hypertension Is Associated with Marked Alterations in Sphingolipid Biology: A Potential Role for Ceramide

AU - Spijkers, Leon J. A.

AU - van den Akker, Rob F. P.

AU - Janssen, Ben J. A.

AU - Debets, Jacques J.

AU - De Mey, Jo G. R.

AU - Stroes, Erik S. G.

AU - van den Born, Bert-Jan H.

AU - Wijesinghe, Dayanjan S.

AU - Chalfant, Charles E.

AU - MacAleese, Luke

AU - Eijkel, Gert B.

AU - Heeren, Ron M. A.

AU - Alewijnse, Astrid E.

AU - Peters, Stephan L. M.

PY - 2011/7/19

Y1 - 2011/7/19

N2 - Background: Hypertension is, amongst others, characterized by endothelial dysfunction and vascular remodeling. As sphingolipids have been implicated in both the regulation of vascular contractility and growth, we investigated whether sphingolipid biology is altered in hypertension and whether this is reflected in altered vascular function. Methods and Findings: In isolated carotid arteries from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats, shifting the ceramide/S1P ratio towards ceramide dominance by administration of a sphingosine kinase inhibitor (dimethylsphingosine) or exogenous application of sphingomyelinase, induced marked endothelium-dependent contractions in SHR vessels (DMS: 1.4 +/- 0.4 and SMase: 2.1 +/- 0.1 mN/mm; n = 10), that were virtually absent in WKY vessels (DMS: 0.0 +/- 0.0 and SMase: 0.6 +/- 0.1 mN/mm; n = 9, p

AB - Background: Hypertension is, amongst others, characterized by endothelial dysfunction and vascular remodeling. As sphingolipids have been implicated in both the regulation of vascular contractility and growth, we investigated whether sphingolipid biology is altered in hypertension and whether this is reflected in altered vascular function. Methods and Findings: In isolated carotid arteries from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats, shifting the ceramide/S1P ratio towards ceramide dominance by administration of a sphingosine kinase inhibitor (dimethylsphingosine) or exogenous application of sphingomyelinase, induced marked endothelium-dependent contractions in SHR vessels (DMS: 1.4 +/- 0.4 and SMase: 2.1 +/- 0.1 mN/mm; n = 10), that were virtually absent in WKY vessels (DMS: 0.0 +/- 0.0 and SMase: 0.6 +/- 0.1 mN/mm; n = 9, p

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DO - 10.1371/journal.pone.0021817

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C2 - 21818267

SN - 1932-6203

VL - 6

SP - 9

JO - PLOS ONE

JF - PLOS ONE

IS - 7

ER -

Hypertension Is Associated with Marked Alterations in Sphingolipid Biology: A Potential Role for Ceramide

Abstract

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