过氧体增殖器激活受体的玛激活剂降低血管光滑肌细胞中的血管酶II型1受体的调节
K Takeda1, T Ichiki, T Tokunou
1Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
Circulation
|October 12, 2000
概括
过氧体增殖器激活受体玛 (PPARgamma) 激活剂减少血管光滑肌细胞中的 ангиотензинII型1受体 (AT(1)-R) 表达. 这种下调可能解释了PPARgamma激活剂如何抑制neointimal形成.
科学领域:
- 血管生物学 血管生物学
- 药理学 药理学是指药理学的学科.
- 分子医学是分子医学.
背景情况:
- 氧酶增殖器激活受体玛 (PPARgamma) 激活剂,如格利塔,改善胰岛素抵抗力,并抑制新因子的形成.
- 通过PPARgamma激活剂抑制新极限形成的确切机制尚未完全理解.
- ангиотензин II (Ang II) 与动脉样硬化,高血压和血管形成术后的新极端扩散有关.
研究的目的:
- 研究PPARgamma激活剂对血管光滑肌细胞 (VSMCs) 中的 ангиотензинII类型1受体 (AT(1)-R) 表达的作用.
主要方法:
- 使用北方斑块和放射性连接体结合试验量化AT(1) -RmRNA和蛋白质水平.
- 评估VSMC对Ang II的反应.
- 路西法酶试验测量AT(1)-R促进体活性和mRNA稳定性.
主要成果:
- 无论是天然的还是合成的PPARgamma激活剂 (15-deoxy-Delta(12,14) -prostaglandin J(2) 和格利塔) 都显著降低了AT(1) -RmRNA和VSMC中的蛋白质表达.
- PPARgamma激活剂减弱了VSMCs对Ang II的反应.
- 抑制AT(1)-R发生在转录水平上,这是由减少促进体活性和不受影响的mRNA稳定性所表明的.
结论:
- 在VSMC中,PPARgamma激活剂有效降低AT(1)-R表达和随后对Ang II的反应.
- 通过PPARgamma激活剂降低AT(1)-R的调节可能是促进抑制新极限形成的关键机制.
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