骨形态蛋白9 减少心脏纤维化,改善心脏功能
Kevin J Morine1, Xiaoying Qiao1, Sam York1
1Molecular Cardiology Research Institute and Division of Cardiology, Department of Medicine, Tufts Medical Center, Boston, MA.
Circulation
|March 1, 2018
概括
通过激活Smad1来抑制心力衰竭中的心肌纤维化. 中和内素增强了BMP9的活性,为心力衰竭患者提供了潜在的治疗策略.
科学领域:
- 心血管生物学
- 分子医学
- 纤维化研究
背景情况:
- 心脏衰竭是全球重要的健康负担.
- 转化生长因子β (TGF-β1) 驱动心脏纤维化,但通过反调节途径进行调节.
- 一个TGF-β家族成员的骨形态蛋白9 (BMP9) 通过Smad1发出信号,而TGF-β核受体内皮蛋白则与BMP9结合并促进Smad3信号传递.
研究的目的:
- 研究BMP9在心脏纤维化中的作用.
- 通过调节Smad1和Smad3通道来确定BMP9是否会抑制心脏纤维化.
- 探索中和内分泌素是否增强了BMP9的活性.
主要方法:
- 在人类心脏纤维细胞和心力衰竭患者中检查BMP9表达.
- 在人类心脏纤维细胞中利用了复合BMP9和小干扰RNA.
- 使用横向大动脉收缩小鼠心力衰竭模型.
- 在体内和体外测试了复合BMP9和内素中和.
主要成果:
- 在心力衰竭患者和心脏纤维细胞中,BMP9的表达升高.
- 在心脏纤维细胞中减弱BMP9的原合成.
- 在小鼠中,BMP9的丧失会加剧心脏纤维化并损害心脏纤维功能.
- 治疗BMP9可以抑制纤维化,改善心脏功能,增加psmad1水平.
- 中和内素增强了BMP9的活性,减少了纤维化,增加了psmad1.
结论:
- 在应对压力过载时,BMP9作为内源性心肌纤维化抑制剂.
- 重组BMP9或内素中和促进了BMP9的活性,限制了心脏纤维化.
- 这些发现表明心力衰竭治疗的新途径.
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