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多中心HFpEF研究确定了与两个离散的心脏蛋白质组签名相关的性别差异
Aleksandra Binek1, Johannes V Janssens1,2, Niveda Sundararaman1
1Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
bioRxiv : the preprint server for biology
|December 25, 2025
概括
保存喷射分数 (HFpEF) 的心力衰竭不是由性别定义的,而是由两个不同的蛋白质组概况定义的. 这些概况揭示了心脏结构,功能和沟通中的分子差异,提供了新的治疗点.
科学领域:
- 心脏病学 心脏病学
- 蛋白质组学是指蛋白质组学.
- 分子生物学分子生物学
背景情况:
- 保存喷射率 (HFpEF) 的心力衰竭越来越普遍,超过了减少喷射率 (HFrEF) 的心力衰竭.
- 在HFpEF表型中观察到的性别差异通常与女性的衰老和代谢问题有关.
研究的目的:
- 对来自HFpEF和HFrEF患者的心脏样本进行多中心蛋白质组分析.
- 为了研究HFpEF蛋白质组中潜在的基于性别的差异.
- 在HFpEF队列中识别不同的分子配置文件.
主要方法:
- 来自HFpEF和HFrEF队列的腹腔心脏组织的蛋白质组分析.
- 利用来自多个机构生物库的组织和临床数据.
- 进行了上游调节器分析,以确定已识别的配置文件的分子驱动因素.
主要成果:
- 与HFrEF相比,HFpEF队列显示出最小的重叠和蛋白质组合的显著异质性.
- 仅仅性别并不能定义一个独特的HFpEF蛋白质组特征.
- 确定了两种不同的HFpEF蛋白质组概况 (集群),不同于性别比例,并以结构/收缩机械和细胞/ECM通信的变化为特征.
结论:
- HFpEF表现出分子异质性,其特点是两个主要的蛋白质组特征,而不是性别特异性.
- 这些发现突出了开发针对性治疗的机会,以解决HFpEF多样化的分子格局.
- 识别特定的分子途径为HFpEF的新药开发提供了途径.
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