在重塑和修复过程中调节心脏功能
Prabhu Mathiyalagan1, Marta Adamiak1, Joshua Mayourian1
1Cardiovascular Research Center, Icahn School of Medicine, Mount Sinai, NY.
Circulation
|July 13, 2018
概括
脂肪质量和与肥胖相关的蛋白质 (FTO) 对心脏功能至关重要. 较低的FTO水平会增加RNA甲基化,损害心脏收缩能力,但FTO恢复会改善心脏病发作后的功能并减少损伤.
科学领域:
- 心血管生物学
- 表观遗传学
- 核糖核酸生物学
背景情况:
- N6-甲基氨酸 (m6A) 在细胞过程中至关重要,但它在心脏中的作用仍未得到充分研究.
- 一种m6A脱甲基酶的FTO蛋白在心脏健康和疾病中的作用受到研究.
研究的目的:
- 阐明FTO和m6A在心脏收缩功能中的作用.
- 了解FTO对心脏平衡,重塑和再生的影响机制.
主要方法:
- 使用人体样本,猪和小鼠模型,以及初级心肌细胞培养.
- 使用病毒载体和小干扰RNA来调节FTO表达.
- 进行m6ARNA免疫沉测序和qPCR以映射和验证m6A修饰.
主要成果:
- 心脏衰竭和缺氧心肌细胞中FTO表达的降低会增加m6A,从而降低收缩能力.
- 在失败的小鼠心脏中恢复FTO可以逆转m6A的增加,并改善心脏功能.
- 在心肌梗塞模型中,FTO脱甲基活性保护心脏转录物免受降解,增强蛋白质表达和减少纤维化,改善血管生成.
结论:
- 对于心力衰竭中心脏收缩而言,FTO依赖心脏m6A甲基组具有重要功能.
- 这项研究为FTO在心脏病中的治疗潜力提供了新的机制见解.
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