PMID- 19771174 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20130704 LR - 20211020 IS - 1874-1924 (Electronic) IS - 1874-1924 (Linking) VI - 3 DP - 2009 Aug 31 TI - Gender-specific modulation of the response to arterial injury by soluble guanylate cyclase alpha1. PG - 98-104 LID - 10.2174/1874192400903010098 [doi] AB - 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 sGCalpha1 subunit (sGCalpha1(-/-)), resulting in a non-functional heterodimer. METHODS: We measured aortic cGMP levels and mRNA transcripts encoding sGC alpha1, alpha2, and beta1 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, sGCalpha1, sGCalpha2, and sGCbeta1 mRNA expression did not differ between groups. (3)H-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. FAU - Vermeersch, Pieter AU - Vermeersch P AD - Vesalius Research Center (VIB) and Cardiac Unit. FAU - Buys, Emmanuel AU - Buys E FAU - Sips, Patrick AU - Sips P FAU - Pokreisz, Peter AU - Pokreisz P FAU - Marsboom, Glenn AU - Marsboom G FAU - Gillijns, Hilde AU - Gillijns H FAU - Pellens, Marijke AU - Pellens M FAU - Dewerchin, Mieke AU - Dewerchin M FAU - Bloch, Kenneth D AU - Bloch KD FAU - Brouckaert, Peter AU - Brouckaert P FAU - Janssens, Stefan AU - Janssens S LA - eng GR - R01 HL070896/HL/NHLBI NIH HHS/United States PT - Journal Article DEP - 20090831 PL - United Arab Emirates TA - Open Cardiovasc Med J JT - The open cardiovascular medicine journal JID - 101480504 PMC - PMC2743853 OTO - NOTNLM OT - Soluble guanylate cyclase OT - gender OT - nitric oxide. OT - vascular remodelling EDAT- 2009/09/23 06:00 MHDA- 2009/09/23 06:01 PMCR- 2009/01/01 CRDT- 2009/09/23 06:00 PHST- 2009/07/13 00:00 [received] PHST- 2009/07/24 00:00 [revised] PHST- 2009/07/27 00:00 [accepted] PHST- 2009/09/23 06:00 [entrez] PHST- 2009/09/23 06:00 [pubmed] PHST- 2009/09/23 06:01 [medline] PHST- 2009/01/01 00:00 [pmc-release] AID - TOCMJ-3-98 [pii] AID - 10.2174/1874192400903010098 [doi] PST - epublish SO - Open Cardiovasc Med J. 2009 Aug 31;3:98-104. doi: 10.2174/1874192400903010098.