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

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

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