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Cardiovascular and pharmacological implications of haem-deficient NO-unresponsive soluble guanylate cyclase knock-in mice

Robrecht Thoonen (UGent) , Anje Cauwels (UGent) , Kelly Decaluwé (UGent) , Sandra Geschka, Robert E Tainsh, Joris Delanghe (UGent) , Tino Hochepied (UGent) , Lode De Cauwer (UGent) , Elke Rogge (UGent) , Sofie Voet (UGent) , et al.
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Abstract
Oxidative stress, a central mediator of cardiovascular disease, results in loss of the prosthetic haem group of soluble guanylate cyclase (sGC), preventing its activation by nitric oxide (NO). Here we introduce Apo-sGC mice expressing haem-free sGC. Apo-sGC mice are viable and develop hypertension. The haemodynamic effects of NO are abolished, but those of the sGC activator cinaciguat are enhanced in apo-sGC mice, suggesting that the effects of NO on smooth muscle relaxation, blood pressure regulation and inhibition of platelet aggregation require sGC activation by NO. Tumour necrosis factor (TNF)-induced hypotension and mortality are preserved in apo-sGC mice, indicating that pathways other than sGC signalling mediate the cardiovascular collapse in shock. Apo-sGC mice allow for differentiation between sGC-dependent and -independent NO effects and between haem-dependent and -independent sGC effects. Apo-sGC mice represent a unique experimental platform to study the in vivo consequences of sGC oxidation and the therapeutic potential of sGC activators.
Keywords
NITRIC-OXIDE SYNTHASE, SEPTIC SHOCK, METHYLENE-BLUE, BLOOD-PRESSURE, HEART-FAILURE, SEVERE SEPSIS, KINASE-I, CGMP, ACTIVATION, IDENTIFICATION

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MLA
Thoonen, Robrecht et al. “Cardiovascular and Pharmacological Implications of Haem-deficient NO-unresponsive Soluble Guanylate Cyclase Knock-in Mice.” NATURE COMMUNICATIONS 6 (2015): n. pag. Print.
APA
Thoonen, R., Cauwels, A., Decaluwé, K., Geschka, S., Tainsh, R. E., Delanghe, J., Hochepied, T., et al. (2015). Cardiovascular and pharmacological implications of haem-deficient NO-unresponsive soluble guanylate cyclase knock-in mice. NATURE COMMUNICATIONS, 6.
Chicago author-date
Thoonen, Robrecht, Anje Cauwels, Kelly Decaluwé, Sandra Geschka, Robert E Tainsh, Joris Delanghe, Tino Hochepied, et al. 2015. “Cardiovascular and Pharmacological Implications of Haem-deficient NO-unresponsive Soluble Guanylate Cyclase Knock-in Mice.” Nature Communications 6.
Chicago author-date (all authors)
Thoonen, Robrecht, Anje Cauwels, Kelly Decaluwé, Sandra Geschka, Robert E Tainsh, Joris Delanghe, Tino Hochepied, Lode De Cauwer, Elke Rogge, Sofie Voet, Patrick Sips, Richard H Karas, Kenneth D Bloch, Marnik Vuylsteke, Johannes-Peter Stasch, Johan Van de Voorde, Emmanuel S Buys, and Peter Brouckaert. 2015. “Cardiovascular and Pharmacological Implications of Haem-deficient NO-unresponsive Soluble Guanylate Cyclase Knock-in Mice.” Nature Communications 6.
Vancouver
1.
Thoonen R, Cauwels A, Decaluwé K, Geschka S, Tainsh RE, Delanghe J, et al. Cardiovascular and pharmacological implications of haem-deficient NO-unresponsive soluble guanylate cyclase knock-in mice. NATURE COMMUNICATIONS. 2015;6.
IEEE
[1]
R. Thoonen et al., “Cardiovascular and pharmacological implications of haem-deficient NO-unresponsive soluble guanylate cyclase knock-in mice,” NATURE COMMUNICATIONS, vol. 6, 2015.
@article{6956870,
  abstract     = {Oxidative stress, a central mediator of cardiovascular disease, results in loss of the prosthetic haem group of soluble guanylate cyclase (sGC), preventing its activation by nitric oxide (NO). Here we introduce Apo-sGC mice expressing haem-free sGC. Apo-sGC mice are viable and develop hypertension. The haemodynamic effects of NO are abolished, but those of the sGC activator cinaciguat are enhanced in apo-sGC mice, suggesting that the effects of NO on smooth muscle relaxation, blood pressure regulation and inhibition of platelet aggregation require sGC activation by NO. Tumour necrosis factor (TNF)-induced hypotension and mortality are preserved in apo-sGC mice, indicating that pathways other than sGC signalling mediate the cardiovascular collapse in shock. Apo-sGC mice allow for differentiation between sGC-dependent and -independent NO effects and between haem-dependent and -independent sGC effects. Apo-sGC mice represent a unique experimental platform to study the in vivo consequences of sGC oxidation and the therapeutic potential of sGC activators.},
  articleno    = {8482},
  author       = {Thoonen, Robrecht and Cauwels, Anje and Decaluwé, Kelly and Geschka, Sandra and Tainsh, Robert E and Delanghe, Joris and Hochepied, Tino and De Cauwer, Lode and Rogge, Elke and Voet, Sofie and Sips, Patrick and Karas, Richard H and Bloch, Kenneth D and Vuylsteke, Marnik and Stasch, Johannes-Peter and Van de Voorde, Johan and Buys, Emmanuel S and Brouckaert, Peter},
  issn         = {2041-1723},
  journal      = {NATURE COMMUNICATIONS},
  keywords     = {NITRIC-OXIDE SYNTHASE,SEPTIC SHOCK,METHYLENE-BLUE,BLOOD-PRESSURE,HEART-FAILURE,SEVERE SEPSIS,KINASE-I,CGMP,ACTIVATION,IDENTIFICATION},
  language     = {eng},
  pages        = {12},
  title        = {Cardiovascular and pharmacological implications of haem-deficient NO-unresponsive soluble guanylate cyclase knock-in mice},
  url          = {http://dx.doi.org/10.1038/ncomms9482},
  volume       = {6},
  year         = {2015},
}

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