降低内分泌素活性限制心脏纤维化,改善心力衰竭的存活率
Navin K Kapur1, Szuhuei Wilson, Adil A Yunis
1Molecular Cardiology Research Institute, Tufts Medical Center, 800 Washington St, Box 80, Boston, MA 02111, USA. Nkapur@tuftsmedicalcenter.org
Circulation
|May 18, 2012
概括
向TGFβ1信号核心受体内,减少心脏纤维化,改善心脏功能和心力衰竭模型中的存活率. 这为心力衰竭患者提供了一种新的治疗策略.
科学领域:
- 心血管生物学 心血管生物学
- 分子医学是分子医学.
- 纤维化研究 纤维化研究
背景情况:
- 心力衰竭是全球死亡的主要原因.
- 转化生长因子-β1 (TGFβ1) 驱动心脏纤维化,恶化心力衰竭.
- 内分泌蛋白,TGFβ1信号核心受体,涉及到血管重塑.
研究的目的:
- 为了研究内林在心脏纤维化中的作用.
- 为了确定是否准内分泌素可以减轻心力衰竭的进展.
主要方法:
- 在人类心力衰竭样本中评估内素表达.
- 利用中和抗体和siRNA阻止TGFβ1在心脏纤维细胞中的信号传递.
- 采用了一种由压力过载引起的心力衰竭的小鼠模型.
- 在体外和体内研究溶性内素的作用.
主要成果:
- 在人类心力衰竭室内,内分泌蛋白表达升高.
- 内分泌蛋白对人类心脏纤维细胞中TGFβ1信号传递至关重要.
- 减少内素减弱心脏纤维化,保持功能,并改善小鼠的生存率.
- 溶性内素抑制了纤维细胞中的TGFβ1信号传递和原合成,并在体内减少纤维化.
结论:
- 内分泌素是TGFβ1信号传递在心脏纤维细胞中的关键媒介.
- 准内分泌蛋白有效降低心脏纤维化.
- 内分泌素抑制为心力衰竭治疗提供了一个有前途的治疗途径.
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