转基因小鼠的左心室重塑与心脏限制过度表达的瘤亡因子
N Sivasubramanian1, M L Coker, K M Kurrelmeyer
1Winters Center for Heart Failure Research, Cardiology Section, Department of Medicine, Veterans Affairs Medical Center, Houston, TX 77030, USA.
Circulation
|August 15, 2001
概括
瘤亡因子 (TNF) 通过改变矩阵金属蛋白酶 (MMP) 和组织金属蛋白酶抑制剂 (TIMP) 的平衡,导致心脏重塑. 这项研究揭示了TNF诱导的MMP/TIMP活性变化如何随着时间的推移影响心肌原蛋白含量.
科学领域:
- 心血管生物学 心血管生物学
- 分子心脏病学分子心脏病学
- 进行心脏重塑.
背景情况:
- 由瘤亡因子 (TNF) 诱导的左心室 (LV) 结构重塑的机制尚不清楚.
- 研究TNF在心脏病理学中的作用对于了解心脏病的进展至关重要.
研究的目的:
- 阐明TNF诱导的LV结构改造背后的机制.
- 确定矩阵金属蛋白酶 (MMP) 和它们的抑制剂 (TIMP) 在这个过程中的作用.
主要方法:
- 生成的转基因小鼠 (MHCsTNF) 具有心脏受限制的TNF过度表达.
- 随着时间的推移,评估了LV重塑,MMP活性,纤维状原蛋白含量和TIMP-1水平.
- 测量TGF-β) 和TGF-β) 蛋白质水平.
主要成果:
- 在MHCsTNF小鼠中呈现出渐进的LV扩张和重塑.
- 早期的重塑显示MMP活性增加和原蛋白减少;后期的阶段显示MMP活性减少和原蛋白增加.
- 随着时间的推移,TIMP-1水平的增加导致了MMP活动/TIMP比率的下降.
- 观察到TGF-β1和TGF-β2水平升高.
结论:
- 在MMP/TIMP平衡的逐渐变化有助于TNF诱导的肌动脉原在LV重塑期间的改变.
- 这些发现为TNF介导的心脏结构变化的分子机制提供了洞察力.
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