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Salvianolic acid B inhibits proliferation and inflammation in vascular smooth muscle cells and endothelial cells through regulating ROS via heme oxygenase-1 induction

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 Salvianolic acid B 에 의해 유도된 heme oxygenase-1 의 ROS 조절을 통한 혈관 평활근 세포의 증식과 혈관 내피세포의 염증 반응 억제 효과 
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Dept. of Medical Science/박사
The reactive oxygen species (ROS)-induced vascular endothelial cells (ECs) dysfunction and vascular smooth muscle cell (VSMCs) proliferation are involved in the development of atherosclerosis and restenosis. Also, ROS is triggered by multiple factors including cytokines such as tumor necrosis factor α (TNF-α) and growth factors such as platelet-derived growth factor (PDGF), which are produced by platelets, VSMCs, and ECs in the injured vascular wall. This study was designed to investigate the effects of salvianolic acid B (Sal B), one of compound in Danshen on HUVECs and VSMCs. Stimulating HUVECs and VSMCs with TNF-α and PDGF-BB in vitro to induce inflammation, proliferation and ROS generation was used to identify the roles of Sal B. Sal B treatment significantly inhibited PDGF-BB-induced cell proliferation and migration, and reduced intracellular ROS generation by PDGF-BB in a dose-dependent manner in VSMCs. Sal B significantly induced heme oxygenase-1 (HO-1) protein expression and inhibited PDGF-BB-induced phosphorylation of AKT by scavenging ROS. Furthermore, Sal B activated the translocation of the transcription factor nuclear factor-E2-related factor 2 (Nrf2) in VSMCs. In HUVECs, Sal B also dramatically induced HO-1 and inhibited TNF-α-induced nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) translocation from cytosol to nucleus and phosphorylation of MAPK by scavenging ROS generation. Our data demonstrated that Sal B inhibits PDGF-BB-induced cell proliferation, migration in VSMCs and TNF-α-induced inflammation in HUVECs by increasing the expression of HO-1 via Nrf2 activation and ROS scavenging, suggesting that Sal B may be a promising agent to prevent atherosclerosis and restenosis.
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2. 학위논문 > 1. College of Medicine > 박사
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