氧化LDL通过对Akt/内皮氧化合成酶通路的抑制作用来抑制血管内皮生长因子诱导的内皮细胞迁移
E Chavakis1, E Dernbach, C Hermann
1Department of Internal Medicine IV, University of Frankfurt, Germany.
Circulation
|April 25, 2001
概括
氧化LDL (oxLDL) 通过抑制Akt/eNOS通路,降低氧化 (NO) 生成,损害内皮细胞迁移. 恢复Akt或eNOS功能可以逆转这种oxLDL诱导的抑制.
科学领域:
- 内皮细胞生物学 内皮细胞生物学
- 血管功能的分子机制
- 脂质代谢和心血管疾病
背景情况:
- 已知氧化低密度脂蛋白 (oxLDL) 抑制内皮细胞 (EC) 迁移.
- 血管内皮生长因子 (VEGF) 通过Akt/蛋白激酶B通路刺激EC迁移,导致内皮氧化合成酶 (eNOS) 的激活和氧化 (NO) 的产生.
研究的目的:
- 调查oxLDL抑制EC迁移的机制.
- 为了确定oxLDL是否影响Akt/eNOS通路和随后的NO生产.
主要方法:
- 在体外"划伤测定"以评估EC迁移.
- 西部斑点分析以评估阿克特酸化状态.
- 使用光指示器量化NO生产.
- 过度表达构成性活跃的Akt和相仿性eNOS结构.
主要成果:
- oxLDL剂量依赖地抑制了VEGF诱导的EC迁移.
- oxLDL导致了Akt的脱和失活.
- oxLDL减少了VEGF诱导的NO产生.
- 过度表达活性Akt或eNOS可以逆转oxLDL的抑制作用.
结论:
- oxLDL通过去酸化Akt来抑制EC迁移,从而损害了eNOS的激活.
- 由于Akt/eNOS信号受损而降低的NO度介导了oxLDL对EC迁移的抑制作用.
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