Endothelial cyclooxygenase-1 paradoxically drives local vasoconstriction and atherogenesis despite underpinning prostacyclin generationCitation formats

  • External authors:
  • Jane A. Mitchell
  • Fisnik Shala
  • Maria Elisa Lopes Pires
  • Rachel Y. Loy
  • Andrew Ravendren
  • Joshua Benson
  • Paula Urquhart
  • Harvey R. Herschman
  • Nicholas S. Kirkby

Standard

Endothelial cyclooxygenase-1 paradoxically drives local vasoconstriction and atherogenesis despite underpinning prostacyclin generation. / Mitchell, Jane A.; Shala, Fisnik; Pires, Maria Elisa Lopes; Loy, Rachel Y.; Ravendren, Andrew; Benson, Joshua; Urquhart, Paula; Nicolaou, Anna; Herschman, Harvey R.; Kirkby, Nicholas S.

In: Science Advances, Vol. 7, No. 12, 19.03.2021, p. eabf6054.

Research output: Contribution to journalArticlepeer-review

Harvard

Mitchell, JA, Shala, F, Pires, MEL, Loy, RY, Ravendren, A, Benson, J, Urquhart, P, Nicolaou, A, Herschman, HR & Kirkby, NS 2021, 'Endothelial cyclooxygenase-1 paradoxically drives local vasoconstriction and atherogenesis despite underpinning prostacyclin generation', Science Advances, vol. 7, no. 12, pp. eabf6054. https://doi.org/10.1126/sciadv.abf6054

APA

Mitchell, J. A., Shala, F., Pires, M. E. L., Loy, R. Y., Ravendren, A., Benson, J., Urquhart, P., Nicolaou, A., Herschman, H. R., & Kirkby, N. S. (2021). Endothelial cyclooxygenase-1 paradoxically drives local vasoconstriction and atherogenesis despite underpinning prostacyclin generation. Science Advances, 7(12), eabf6054. https://doi.org/10.1126/sciadv.abf6054

Vancouver

Mitchell JA, Shala F, Pires MEL, Loy RY, Ravendren A, Benson J et al. Endothelial cyclooxygenase-1 paradoxically drives local vasoconstriction and atherogenesis despite underpinning prostacyclin generation. Science Advances. 2021 Mar 19;7(12):eabf6054. https://doi.org/10.1126/sciadv.abf6054

Author

Mitchell, Jane A. ; Shala, Fisnik ; Pires, Maria Elisa Lopes ; Loy, Rachel Y. ; Ravendren, Andrew ; Benson, Joshua ; Urquhart, Paula ; Nicolaou, Anna ; Herschman, Harvey R. ; Kirkby, Nicholas S. / Endothelial cyclooxygenase-1 paradoxically drives local vasoconstriction and atherogenesis despite underpinning prostacyclin generation. In: Science Advances. 2021 ; Vol. 7, No. 12. pp. eabf6054.

Bibtex

@article{ad3e10bf9b3c4af4b82f53e9c8b9ec84,
title = "Endothelial cyclooxygenase-1 paradoxically drives local vasoconstriction and atherogenesis despite underpinning prostacyclin generation",
abstract = "Endothelial cyclooxygenase-1–derived prostanoids, including prostacyclin, have clear cardioprotective roles associated with their anti-thrombotic potential but have also been suggested to have paradoxical pathological activities within arteries. To date it has not been possible to test the importance of this because no models have been available that separate vascular cyclooxygenase-1 products from those generated elsewhere. Here, we have used unique endothelial-specific cyclooxygenase-1 knockout mice to show that endothelial cyclooxygenase-1 produces both protective and pathological products. Functionally, however, the overall effect of these was to drive pathological responses in the context of both vasoconstriction in vitro and the development of atherosclerosis and vascular inflammation in vivo. These data provide the first demonstration of a pathological role for the vascular cyclooxygenase-1 pathway, highlighting its potential as a therapeutic target. They also emphasize that, across biology, the role of prostanoids is not always predictable due to unique balances of context, products, and receptors.",
author = "Mitchell, {Jane A.} and Fisnik Shala and Pires, {Maria Elisa Lopes} and Loy, {Rachel Y.} and Andrew Ravendren and Joshua Benson and Paula Urquhart and Anna Nicolaou and Herschman, {Harvey R.} and Kirkby, {Nicholas S.}",
year = "2021",
month = mar,
day = "19",
doi = "10.1126/sciadv.abf6054",
language = "English",
volume = "7",
pages = "eabf6054",
journal = "Science Advances",
issn = "2375-2548",
publisher = "American Association for the Advancement of Science (A A A S)",
number = "12",

}

RIS

TY - JOUR

T1 - Endothelial cyclooxygenase-1 paradoxically drives local vasoconstriction and atherogenesis despite underpinning prostacyclin generation

AU - Mitchell, Jane A.

AU - Shala, Fisnik

AU - Pires, Maria Elisa Lopes

AU - Loy, Rachel Y.

AU - Ravendren, Andrew

AU - Benson, Joshua

AU - Urquhart, Paula

AU - Nicolaou, Anna

AU - Herschman, Harvey R.

AU - Kirkby, Nicholas S.

PY - 2021/3/19

Y1 - 2021/3/19

N2 - Endothelial cyclooxygenase-1–derived prostanoids, including prostacyclin, have clear cardioprotective roles associated with their anti-thrombotic potential but have also been suggested to have paradoxical pathological activities within arteries. To date it has not been possible to test the importance of this because no models have been available that separate vascular cyclooxygenase-1 products from those generated elsewhere. Here, we have used unique endothelial-specific cyclooxygenase-1 knockout mice to show that endothelial cyclooxygenase-1 produces both protective and pathological products. Functionally, however, the overall effect of these was to drive pathological responses in the context of both vasoconstriction in vitro and the development of atherosclerosis and vascular inflammation in vivo. These data provide the first demonstration of a pathological role for the vascular cyclooxygenase-1 pathway, highlighting its potential as a therapeutic target. They also emphasize that, across biology, the role of prostanoids is not always predictable due to unique balances of context, products, and receptors.

AB - Endothelial cyclooxygenase-1–derived prostanoids, including prostacyclin, have clear cardioprotective roles associated with their anti-thrombotic potential but have also been suggested to have paradoxical pathological activities within arteries. To date it has not been possible to test the importance of this because no models have been available that separate vascular cyclooxygenase-1 products from those generated elsewhere. Here, we have used unique endothelial-specific cyclooxygenase-1 knockout mice to show that endothelial cyclooxygenase-1 produces both protective and pathological products. Functionally, however, the overall effect of these was to drive pathological responses in the context of both vasoconstriction in vitro and the development of atherosclerosis and vascular inflammation in vivo. These data provide the first demonstration of a pathological role for the vascular cyclooxygenase-1 pathway, highlighting its potential as a therapeutic target. They also emphasize that, across biology, the role of prostanoids is not always predictable due to unique balances of context, products, and receptors.

U2 - 10.1126/sciadv.abf6054

DO - 10.1126/sciadv.abf6054

M3 - Article

VL - 7

SP - eabf6054

JO - Science Advances

JF - Science Advances

SN - 2375-2548

IS - 12

ER -