Cardiovascular and pharmacological implications of haem-deficient NO-unresponsive soluble guanylate cyclase knock-in mice
- Author
- 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, Patrick Sips (UGent) , Richard H Karas, Kenneth D Bloch, Marnik Vuylsteke (UGent) , Johannes-Peter Stasch, Johan Van de Voorde (UGent) , Emmanuel S Buys and Peter Brouckaert (UGent)
- Organization
- 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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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-6956870
- MLA
- Thoonen, Robrecht, et al. “Cardiovascular and Pharmacological Implications of Haem-Deficient NO-Unresponsive Soluble Guanylate Cyclase Knock-in Mice.” NATURE COMMUNICATIONS, vol. 6, 2015, doi:10.1038/ncomms9482.
- APA
- Thoonen, R., Cauwels, A., Decaluwé, K., Geschka, S., Tainsh, R. E., Delanghe, J., … Brouckaert, P. (2015). Cardiovascular and pharmacological implications of haem-deficient NO-unresponsive soluble guanylate cyclase knock-in mice. NATURE COMMUNICATIONS, 6. https://doi.org/10.1038/ncomms9482
- 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. https://doi.org/10.1038/ncomms9482.
- 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. doi:10.1038/ncomms9482.
- 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://doi.org/10.1038/ncomms9482}}, volume = {{6}}, year = {{2015}}, }
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