Abstract WMP83: cGMP-Dependent Protein Kinase I in Smooth Muscle Cells Protects Against Stroke in Female Mice

• Published in: Stroke (1970) 2019-02, Vol.50 (Suppl_1)
• Main Authors: Shvedova, Maria, Roberts, Jesse D, Huang, Paul L, Feil, Robert, Atochin, Dmitriy N
• Format: Article
• Language: English
• ISSN: 0039-2499; 1524-4628
• DOI: 10.1161/str.50.suppl_1.WMP83

Abstract only Introduction: The role of cGMP-dependent protein kinase I (cGKI) in regulating vascular smooth muscle cells (SMC) during stroke has not been completely clarified. We showed that SMC cGKI has protective effect against stroke in male mice. To elucidate whether cGKI in SMC renders its protective effect on stroke outcome by sex-dependent mechanism, we conducted study on female mice. Animals: We used a novel tamoxifen-inducible SMC-specific gene knockout mice, that expresses CreER T2 recombinase under the control of smooth muscle alpha-actin promoter. SMA-CreER T2 _cGKIfloxflox adult 12-14 weeks-old female mice after tamoxifen (TAM) administration (100 μl TAM solution (1 mg/ml) i.p. per day for 5 consecutive days at the age 5-6 weeks) were used as experimental animals (cGKI SMKO mice). Control animals consisted of three types of female mice: (1) C57BL/6 (WT) mice without TAM treatment; (2) SMA-CreER T2 _cGKIfloxflox mice without TAM treatment (cGKI control); (3) cGKIfloxflox mice (without SMA-CreER T2 transgene) treated with TAM (cGKI control TAM). Methods: Mice (n=12/group) were anesthetized (1.5% of isoflurane in 30% of O 2 and 70% of N 2 O), body temperature was maintained (36.5-37.0 0 C) during 30-min filament-mediated middle cerebral artery occlusion (MCAO) and 30 min of reperfusion. Cerebral laser-Doppler flowmetry was utilized during the surgery to evaluate the regional cerebral blood flow (CBF). Results: The cGKI SMKO mice revealed greater cerebral infarct volume (93±12 mm 3 , Mean±SD) than WT (64±14), cGKI control (62±14), and cGKI control TAM (68±10) mice (TTC staining, indirect calculation, p