title: Gender-specific modulation of the response to arterial injury by soluble guanylate cyclase α1.
abstract: OBJECTIVE
  Soluble guanylate cyclase (sGC), a heterodimer composed of alpha and beta 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Vesalius Research Center (VIB) and Cardiac Unit.
authors.forename: Pieter
authors.initials: P
authors.lastname: Vermeersch
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Buys
authors.forename: Patrick
authors.initials: P
authors.lastname: Sips
authors.forename: Peter
authors.initials: P
authors.lastname: Pokreisz
authors.forename: Glenn
authors.initials: G
authors.lastname: Marsboom
authors.forename: Hilde
authors.initials: H
authors.lastname: Gillijns
authors.forename: Marijke
authors.initials: M
authors.lastname: Pellens
authors.forename: Mieke
authors.initials: M
authors.lastname: Dewerchin
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Bloch
authors.forename: Peter
authors.initials: P
authors.lastname: Brouckaert
authors.forename: Stefan
authors.initials: S
authors.lastname: Janssens