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在iPSC衍生的血管光滑肌细胞中识别疾病相关的基于性别的蛋白质差异

Nethika R Ariyasinghe¹, Divya Gupta¹, Sean Escopete¹

¹Advanced Clinical Biosystems Research Institute, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.

International journal of molecular sciences

|January 11, 2025

概括

这项研究揭示了血管光滑肌细胞的基于性别的蛋白质组差异,突出了心血管疾病治疗的潜在新点. 这些在人类细胞中的发现提供了超越动物模型的洞察力.

科学领域:

心血管生物学心血管生物学
蛋白质组学是指蛋白质组学.
细胞和分子医学细胞和分子医学

背景情况:

心血管疾病的患病率因性别而异,但基本的血管机制尚不清楚.
动物模型提供了洞察力,但在转化为人类生物学方面存在局限性.
研究人类血管细胞中的基于性别的差异对于理解心血管病理生理学至关重要.

研究的目的:

在诱导多能干细胞 (iPSC) 衍生的血管光滑肌细胞 (VSMCs) 中识别基于性别的蛋白质差异.
探索染色体性别对与心血管疾病相关的蛋白质基因表型的影响.
验证iPSC衍生的VSMC作为研究基于性别的血管生物学模型.

主要方法:

利用从健康的男性和女性捐赠者获得的iPSC衍生的VSMC.
进行蛋白质组分析以确定细胞通路中的基于性别的差异.
对比iPSC衍生的VSMCs与主性大动脉光滑肌细胞的蛋白质特征.

主要成果:

差异化的iPSC衍生的VSMCs与主要大动脉光滑肌细胞的蛋白质结构密切相似.
确定了包括ATP结合,糖原代谢和卡德林结合在内的途径的显著基于性别的蛋白质差异.
发现了自体染色体上蛋白质的基于性别的调节,影响蛋白质表达.

结论:

来自iPSC的VSMC是研究基于性别的心血管病理生理学的生物学相关模型.
已识别的途径和蛋白质为开发心血管疾病的性别特异性药理学标提供了潜力.
性染色体和自体染色体在血管细胞内的基于性别的蛋白质调节中发挥作用.

关键词:

疾病模型的疾病模型.这些是iPSCs.蛋白质组学蛋白质组学性别差异的性别差异.血管光滑肌肉细胞的细胞.

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