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在iPSC衍生的血管光滑肌肉中识别疾病相关的基于性别的蛋白质组差异

Nethika R Ariyasinghe, Divya Gupta, Sean Escopete

bioRxiv : the preprint server for biology

|August 30, 2024

概括

心血管疾病的风险因性别而异. 研究人员确定了由诱导多能干细胞 (iPSC) 衍生出的血管光滑肌细胞中的性别特异性蛋白质差异,揭示了性别特异性治疗的潜在新点.

科学领域:

蛋白质组学是指蛋白质组学.
血管生物学血管生物学
心血管疾病研究研究

背景情况:

心血管疾病 (CVD) 的患病率因性别而异,但根本的血管机制尚未完全理解.
动物模型提供了洞察力,但并不总是转化为人类生物学.
诱导多能干细胞 (iPSCs) 提供了一个与人类相关的模型系统.

研究的目的:

为了研究染色体性别对血管光滑肌肉细胞中蛋白质基因表型的影响.
确定基于性别的蛋白质组差异及其在心血管病理生理学中的潜在作用.
验证iPSC衍生的血管光滑肌细胞作为研究心血管疾病性别差异的模型.

主要方法:

从健康的男性和女性捐赠者中分化的iPSC转化为血管光滑肌肉细胞.
进行蛋白质组分析以比较基于性别的差异.
与初级大动脉光滑肌细胞相比,验证了差异化的细胞蛋白质特征.

主要成果:

差异化IPSC衍生的血管光滑肌细胞表现出类似于主性大动脉光滑肌细胞的蛋白质特征.
在与ATP结合,糖原代谢和卡德林结合相关的途径中发现了显著的基于性别的蛋白质基因差异.
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.
确定了与心脏病风险相关的特定的性别特异性蛋白质标记物 (例如PCK2,MTOR,IGFBP2,PTGR2,SULTE1).

结论:

来自iPSC的血管平滑肌细胞是研究心血管健康的基于性别差异的生物学相关模型.
血管光滑肌细胞中的基于性别的蛋白质差异有助于心血管病理生理学.
对已识别的途径的进一步研究可能会揭示心血管疾病的性别特异性药理标.

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