阿托瓦斯塔丁在子大动脉中抑制高胆固醇血引起的细胞增殖和骨基质产生
Nalini M Rajamannan1, Malayannan Subramaniam, Margaret Springett
1Division of Cardiology, Department of Medicine, Northwestern University Medical School, Chicago, Ill 60611, USA. n.rajamannan@northwestern.edu
Circulation
|June 5, 2002
概括
高胆固醇血症导致大动脉动脉硬化和子的骨类变化. 阿托瓦斯塔丁治疗逆转了这些效应,表明了对大动脉狭窄的治疗点.
科学领域:
- 心血管生物学 心血管生物学
- 动脉样硬化研究 动脉样硬化研究
- 翻译医学是一种翻译医学.
背景情况:
- 由于缺乏实验模型,大动脉狭窄的细胞原因尚不清楚.
- 大动脉膜中的动脉样硬化和骨基质表达被假定是高胆固醇血症的次要原因.
- 目前正在研究阿托尔瓦斯塔丁改变这种转变的潜力.
研究的目的:
- 为了研究大动脉狭窄的细胞机制.
- 为了确定高胆固醇血是否会诱导动脉样硬化和大动脉膜骨的形成.
- 评估阿托瓦斯塔丁对这些病理变化的作用.
主要方法:
- 开发了一个高胆固醇贫血的子模型 (n=48) 与对照组,胆固醇养组和阿托瓦斯塔丁治疗组.
- 通过组织学染色 (H&E,Masson三色素) 和免疫染色 (RAM 11,PCNA,骨质疏松素) 分析了大动脉.
- 通过RT-PCR评估血清标记物 (胆固醇,hsCRP) 和骨质细胞标记物的基因表达 (性酸酶,骨质,Cbfa-1).
主要成果:
- 胆固醇养的子显示出大动脉的巨细胞 (RAM 11),增殖 (PCNA),骨质和骨质母细胞标记物的增加.
- 高胆固醇血清导致血清胆固醇和hsCRP水平升高.
- 阿托瓦斯塔丁治疗显著降低了PCNA,RAM 11,骨质和骨质母细胞基因标记物,但没有hsCRP.
结论:
- 实验性高胆固醇血会诱导大动脉膜的扩散性,类似动脉样过程.
- 这一过程涉及转化为类似骨质母细胞的表型,由增加的骨基质蛋白质证明.
- 阿托瓦斯塔丁有效地抑制了大动脉中的这种病理转变.
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