降低固体生产的硫化加速动脉样硬化
Sarathi Mani1, Hongzhu Li, Ashley Untereiner
1Department of Biology, Lakehead University, Thunder Bay, ON, Canada.
Circulation
|May 25, 2013
概括
减少硫化 (H2S) 的产生加速动脉样硬化. 补充NaHS可以在缺乏cystathionine γ-lyase (CSE) 的小鼠中预防饮食诱导的动脉样硬化,强调CSE/H2S途径作为治疗标.
科学领域:
- 心血管生物学 心血管生物学
- 代谢性疾病研究研究
- 动脉样硬化病原体的产生
背景情况:
- 囊氨酸γ-酶 (CSE) 对于心血管系统内固有的硫化 (H2S) 生产至关重要.
- 在小鼠中,CSE缺乏导致H2S水平降低,血压升高和血管松功能受损.
- 改变内源H2S代谢在动脉样硬化中的直接作用尚不清楚.
研究的目的:
- 调查内源性H2S产量减少在动脉样硬化发展中的因果作用.
- 评估针对动脉样硬化中CSE/H2S通路的治疗潜力.
主要方法:
- 六周大的CSE基因淘汰和野生型小鼠在12周内被食控制或异质性饮食.
- 分析包括血脂质谱,同氨酸,血压,氧化应激,病变大小,细胞增殖和粘附分子表达.
- 用NAHS,N-乙半氨酸或ezetimibe治疗CSE淘汰的小鼠;还研究了双重淘汰 (CSE和apolipoprotein E).
主要成果:
- 接受异质性饮食的CSE绝杀性小鼠表现出早期脂肪链病变,高胆固醇和LDL,高血糖血,氧化应激增加和大动脉内脏增多.
- 在CSE淘汰赛小鼠中,NaHS治疗改善了饮食诱导的动脉样硬化,而N-乙半氨酸和ezetimibe则没有.
- 与单次淘汰相比,CSE和阿波利波蛋白E基因的联合淘汰会加剧动脉样硬化.
结论:
- 通过CSE途径合成的内源H2S通过减少内密增殖和粘附分子表达来防止动脉动脉损伤.
- 减少内源H2S的产生促进了血管重塑,加速了动脉样硬化的发展.
- CSE/H2S通路代表了预防动脉样硬化的重要治疗目标.
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