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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dc.contributor.author Vermeersch, Pieter
dc.contributor.author Pokreisz, Peter
dc.contributor.author Marsboom, Glenn
dc.contributor.author Gillijns, Hilde
dc.contributor.author Pellens, Marijke
dc.contributor.author Dewerchin, Mieke
dc.contributor.author Brouckaert, Peter
dc.contributor.author Janssens, Stefan
dc.contributor.author Buys, Emmanuel
dc.contributor.author Sips, Patrick
dc.contributor.author Bloch, Kenneth Daniel
dc.date.accessioned 2011-04-08T16:22:18Z
dc.date.issued 2009
dc.identifier.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. en_US
dc.identifier.issn 1874-1924 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:4817626
dc.description.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. en_US
dc.language.iso en_US en_US
dc.publisher Bentham Open en_US
dc.relation.isversionof doi://10.2174/1874192400903010098 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2743853/pdf/ en_US
dash.license LAA
dc.subject guanylate cyclase en_US
dc.subject gender en_US
dc.subject vascular remodelling en_US
dc.subject citric oxide en_US
dc.title Gender-Specific Modulation of the Response to Arterial Injury by Soluble Guanylate Cyclase α1 en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal The Open Cardiovascular Medicine Journal en_US
dash.depositing.author Buys, Emmanuel
dc.date.available 2011-04-08T16:22:18Z
dash.affiliation.other HMS^Anaesthesia-Massachusetts General Hospital en_US

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