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- W3175961188 abstract "Mechanical stretch-sensitive protein synthesis in vascular smooth muscle (VSMC) is the basis of hypertensive vascular disease. Its mechanisms involve activation of different signaling pathways including Rho/ROCK, MAPK, actin cytoskeleton remolding and production of leptin. However the detailed signaling pathways are still not clear. Recent studies have linked leptin to cardiovascular disease such as hypertension and vascular hypertrophy. In the present study, we used rat portal vein (RPV) organ culture to investigate whether atorvastatin (12 mM) can ameliorate the effect of mechanical stretch on leptin synthesis, the reactive oxygen species (ROS) production, ERK1/2 and SRF activation. RPV were either unstretched (control) or stretched by weight at different time intervals (0, 15, 30, 60 min and 24 hr). Protein expression was assessed using Western blotting and immunohistochemistry methods. Mechanical stretch significantly up-regulated leptin's expression, ERK1/2, RhoA and cofilin phosphorylation. Atrovastatin significantly attenuated mechanical stretch-induced leptin expression, ERK1/2 and cofilin phosphorylation and ROS production. Exposing the RPV to mechanical stretch for 1h significantly increased nuclear translocation of the transcription factor SRF which was attenuated by the co-administration of an anti-leptin receptor antibody and the atrovastatin. Moreover, mechanical stretch-induced VSMC hypertrophy and protein synthesis were inhibited by pre-treatment with atorvastatin.Our results indicate that the therapeutic effect the antihypertensive drug “atrovastatin” in attenuating vascular remodeling might be through the inhibition of leptin and ROS production, ERK1/2, SRF and cofilin phosphorylation." @default.
- W3175961188 created "2021-07-05" @default.
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- W3175961188 date "2015-04-01" @default.
- W3175961188 modified "2023-10-16" @default.
- W3175961188 title "Atorvastatin‐Attenuates Mechanical Stretch‐Induced Vascular Smooth Muscle Remodeling" @default.
- W3175961188 doi "https://doi.org/10.1096/fasebj.29.1_supplement.948.5" @default.
- W3175961188 hasPublicationYear "2015" @default.
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