Gender-Specific Modulation of the Response to Arterial Injury by Soluble Guanylate Cyclase α1

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Gender-Specific Modulation of the Response to Arterial Injury by Soluble Guanylate Cyclase α1

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Title: Gender-Specific Modulation of the Response to Arterial Injury by Soluble Guanylate Cyclase α1
Author: Vermeersch, Pieter; Pokreisz, Peter; Marsboom, Glenn; Gillijns, Hilde; Pellens, Marijke; Dewerchin, Mieke; Brouckaert, Peter; Janssens, Stefan; Buys, Emmanuel; Sips, Patrick; Bloch, Kenneth Daniel

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

Citation: Vermeersch, Pieter, Emmanuel Buys, Patrick Sips, Peter Pokreisz, Glenn Marsboom, Hilde Gillijns, Marijke Pellens, and et al. 2009. Gender-specific modulation of the response to arterial injury by soluble guanylate cyclase α1. The Open Cardiovascular Medicine Journal 3: 98-104.
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Abstract: Objective: Soluble guanylate cyclase (sGC), a heterodimer composed of α and β subunits, synthesizes cGMP in response to nitric oxide (NO). NO modulates vascular tone and structure but the relative contributions of cGMP-dependent versus cGMP-independent mechanisms remain uncertain. We studied the response to vascular injury in male (M) and female (F) mice with targeted deletion of exon 6 of the sGCα1 subunit (sGCα1-/-), resulting in a non-functional heterodimer. Methods: We measured aortic cGMP levels and mRNA transcripts encoding sGC α1, α2, and β1 subunits in wild type (WT) and sGCa1-/- mice. To study the response to vascular injury, BrdU-incorporation and neointima formation (maximum intima to media (I/M) ratio) were determined 5 and 28 days after carotid artery ligation, respectively. Results: Aortic cGMP levels were 4-fold higher in F than in M mice in both genotypes, and, within each gender, 4-fold higher in WT than in sGCa1-/-. In contrast, sGCα1, sGCα2, and sGCβ1 mRNA expression did not differ between groups. 3H-thymidine incorporation in cultured sGCa1-/- smooth muscle cells (SMC) was 27%±12% lower than in WT SMC and BrdU-incorporation in carotid arteries 5 days after ligation was significantly less in sGCa1-/- M than in WT M. Neointima area and I/M 28 days after ligation were 65% and 62% lower in sGCa1-/- M than in WT M mice (p<0,05 for both) but were not different in F mice. Conclusion: Functional deletion of sGCa1 resulted in reduced cGMP levels in male sGCa1-/- mice and a gender-specific effect on the adaptive response to vascular injury.
Published Version: doi://10.2174/1874192400903010098
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2743853/pdf/
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:4817626

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