Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China.
Mol Cell Biochem. 2014 Mar;388(1-2):75-84. doi: 10.1007/s11010-013-1900-7. Epub 2013 Nov 28.
Vascular remodeling is characterized by the aggregation of vascular smooth muscle cells (VSMCs) in intima. Previous studies have demonstrated that dehydroepiandrosterone (DHEA), a steroid hormone, can reverse vascular remodeling. However, it is still far clear that whether and how DHEA participates in the modulation of VSMCs activation and vascular remodeling. VSMCs were obtained from the thoracic aorta of SD rats. Cell proliferation was evaluated by CCK-8 assay and BrdU assay. To measure VSMCs migration activity, a transwell chamber assay was performed. Quantitative real-time RT-PCR and western blot were used to explore the molecular mechanisms. ROS generation by VSMCs was measured by DCF fluorescence. NADPH oxidase activity and SOD activity were measured by the corresponding kits. NF-κB activity was detected by NF-κB luciferase reporter gene assay. A rat carotid artery balloon injury model was built to evaluate the neointimal formation, and plasma PGF2 was measured by ELISA. Our results showed that DHEA significantly inhibited VSMCs proliferation after angiotensin (Ang II) stimulation by down-regulation of NADPH oxidase activity and ERK1/2 phosphorylation. Ang II can increase IL-6 and MCP-1 expression, but DHEA reverses these changes via inhibiting p38-MAPK/NF-κB (p65) signaling pathway. DHEA has no significant effects on VSMCs phenotype transition, but can reduce the neointimal to media area ratio after balloon injury. DHEA can alleviate oxidative stress and inflammation in VSMCs via ERK1/2 and NF-κB signaling pathway, but has no effect on VSMCs phenotype transition. Furthermore, DHEA attenuates VSMCs activation and neointimal formation after carotid injury in vivo. Taken together, DHEA might be a promising treatment for vascular injury under pathological condition.
血管重构的特征是血管平滑肌细胞（VSMCs）在内膜中的聚集。先前的研究表明，一种类固醇激素脱氢表雄酮（DHEA）可以逆转血管重构。然而，目前尚不清楚 DHEA 是否以及如何参与调节 VSMCs 的激活和血管重构。从 SD 大鼠的胸主动脉中获得 VSMCs。通过 CCK-8 测定和 BrdU 测定评估细胞增殖。通过 Transwell 室测定测量 VSMCs 迁移活性。通过定量实时 RT-PCR 和 Western blot 探索分子机制。通过 DCF 荧光测量 VSMCs 中的 ROS 生成。通过相应的试剂盒测量 NADPH 氧化酶活性和 SOD 活性。通过 NF-κB 荧光素酶报告基因测定检测 NF-κB 活性。构建大鼠颈动脉球囊损伤模型以评估新生内膜形成，并通过 ELISA 测量血浆 PGF2。我们的结果表明，DHEA 通过下调 NADPH 氧化酶活性和 ERK1/2 磷酸化，显著抑制血管紧张素（Ang II）刺激后的 VSMCs 增殖。Ang II 可以增加 IL-6 和 MCP-1 的表达，但 DHEA 通过抑制 p38-MAPK/NF-κB（p65）信号通路逆转这些变化。DHEA 对 VSMCs 表型转化没有显著影响，但可以降低球囊损伤后的新生内膜与中膜面积比。DHEA 通过 ERK1/2 和 NF-κB 信号通路减轻 VSMCs 中的氧化应激和炎症，但对 VSMCs 表型转化没有影响。此外，DHEA 可减轻体内颈动脉损伤后 VSMCs 的激活和新生内膜形成。总之，DHEA 可能是一种有前途的治疗病理性血管损伤的方法。
