高水静压通过p300/p53/Smad3通路参与心房纤维化
Shenghuan Yu1, Long Zeng1, Fang Rao1,2
1Guangdong Provincial Key Laboratory of Clinical Pharmacology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, P.R. China.
概括
高水静压是高血压的一个因素,通过激活p300/p53/Smad3通路,促进心房纤维化,增加心房动的风险.
科学领域:
- 心血管生物学 心血管生物学
- 疾病的分子机制.
- 纤维化研究 纤维化研究
背景情况:
- 高血压是心房动 (AF) 的关键危险因素.
- 与高血压相关的高水静压与心房纤维化有关,但其机制尚不清楚.
- 已知p300/p53/Smad3通路参与心房纤维化.
研究的目的:
- 通过p300/p53/Smad3通路调查高水静压是否会促进心房纤维化.
- 在高血压条件下检查心脏组织和纤维细胞中p300/p53/Smad3通路的表达.
主要方法:
- 对p300/p53/Smad3通路和纤维化因子表达在人类和小鼠心脏组织 (左心房附属体) 和心房纤维细胞的分析.
- 在小鼠心房纤维细胞中对p300和p53进行基因操纵 (敲除/过度表达).
- 用黄素 (Cur) 治疗,以评估其对该途径的影响.
主要成果:
- 在AF和高血压患者和高血压小鼠中观察到p300/p53/Smad3和纤维化因子的增加表达.
- 高水静压和p300过度表达对纤维细胞中的通路和纤维化因子进行了上调.
- 黄素治疗和p300敲击逆转了这些上调表达;p53操纵显示了相应的效果.
结论:
- 高水静压通过激活p300/p53/Smad3通路促进心房纤维化.
- 这种激活增加了对心房的易感性.
- 准p300/p53/Smad3通路可能为高血压引起的AF提供治疗潜力.
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