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Gender-specific modulation of the response to arterial injury by soluble guanylate cyclase α1.

Vermeersch P, Buys E, Sips P, Pokreisz P, Marsboom G, Gillijns H, Pellens M, Dewerchin M, Bloch KD, Brouckaert P, Janssens S - Open Cardiovasc Med J (2009)

Bottom Line: NO modulates vascular tone and structure but the relative contributions of cGMP-dependent versus cGMP-independent mechanisms remain uncertain.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.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.

View Article: PubMed Central - PubMed

Affiliation: Vesalius Research Center (VIB) and Cardiac Unit.

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.

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.

No MeSH data available.


Related in: MedlinePlus

Vascular cGMP levels in WT (open bars) and sGCα1-/- (closed bars) male mice (M) and female mice (F). Aortic cGMP levels were 4-fold higher in F than in M mice in either genotype, and, within each gender, 4-fold higher in WT than in sGCα1-/- mice (* p<0.05 vs. all).
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Figure 2: Vascular cGMP levels in WT (open bars) and sGCα1-/- (closed bars) male mice (M) and female mice (F). Aortic cGMP levels were 4-fold higher in F than in M mice in either genotype, and, within each gender, 4-fold higher in WT than in sGCα1-/- mice (* p<0.05 vs. all).

Mentions: To investigate gender and genotype-dependent effects on sGC gene function, unstimulated aortic cGMP levels were measured. cGMP levels were 4-fold higher in females than in males in both genotypes (p<0.05 each), and, within each gender, 4-fold higher in WT than in sGCα1-/- (p<0.05 each, Fig. 2).


Gender-specific modulation of the response to arterial injury by soluble guanylate cyclase α1.

Vermeersch P, Buys E, Sips P, Pokreisz P, Marsboom G, Gillijns H, Pellens M, Dewerchin M, Bloch KD, Brouckaert P, Janssens S - Open Cardiovasc Med J (2009)

Vascular cGMP levels in WT (open bars) and sGCα1-/- (closed bars) male mice (M) and female mice (F). Aortic cGMP levels were 4-fold higher in F than in M mice in either genotype, and, within each gender, 4-fold higher in WT than in sGCα1-/- mice (* p<0.05 vs. all).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2743853&req=5

Figure 2: Vascular cGMP levels in WT (open bars) and sGCα1-/- (closed bars) male mice (M) and female mice (F). Aortic cGMP levels were 4-fold higher in F than in M mice in either genotype, and, within each gender, 4-fold higher in WT than in sGCα1-/- mice (* p<0.05 vs. all).
Mentions: To investigate gender and genotype-dependent effects on sGC gene function, unstimulated aortic cGMP levels were measured. cGMP levels were 4-fold higher in females than in males in both genotypes (p<0.05 each), and, within each gender, 4-fold higher in WT than in sGCα1-/- (p<0.05 each, Fig. 2).

Bottom Line: NO modulates vascular tone and structure but the relative contributions of cGMP-dependent versus cGMP-independent mechanisms remain uncertain.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.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.

View Article: PubMed Central - PubMed

Affiliation: Vesalius Research Center (VIB) and Cardiac Unit.

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.

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.

No MeSH data available.


Related in: MedlinePlus