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

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

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Title: Cardiovascular and pharmacological implications of haem-deficient NO-unresponsive soluble guanylate cyclase knock-in mice
Author: Thoonen, Robrecht; Cauwels, Anje; Decaluwe, Kelly; Geschka, Sandra; Tainsh, Robert; Delanghe, Joris; Hochepied, Tino; De Cauwer, Lode; Rogge, Elke; Voet, Sofie; Sips, Patrick; Karas, Richard H.; Bloch, Kenneth; Vuylsteke, Marnik; Stasch, Johannes-Peter; Van de Voorde, Johan; Buys, Emmanuel; Brouckaert, Peter

Note: Order does not necessarily reflect citation order of authors.

Citation: Thoonen, Robrecht, Anje Cauwels, Kelly Decaluwe, 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: 8482. doi:10.1038/ncomms9482.
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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.
Published Version: doi:10.1038/ncomms9482
Other Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4699393/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:29729414
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