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氨酸通过对巨细胞的剂量依赖MTOR激活加速动脉样硬化

Xiangyu Zhang^1,2, Ali Ajam^1,2, Ziyang Liu^1,2

¹Department of Medicine and Vascular Medicine Institute, University of Pittsburgh School of Medicine and UPMC, Pittsburgh, PA, USA.

|March 6, 2025

概括

过多的食蛋白质,特别是白素,可以通过破坏巨细胞功能和抑制保护性自细胞来促进心血管疾病 (CVD). 这项研究强调了白氨酸.

科学领域:

心血管科学心血管科学
代谢信号传递代谢信号传递
营养免疫学营养免疫学

背景情况:

饮食中的脂质已知是导致心血管疾病 (CVD) 的贡献者.
饮食中的蛋白质通常被认为有利于代谢健康和体重管理.
新兴的流行病学数据表明,与过度摄入蛋白质相关的潜在心血管疾病风险.

研究的目的:

研究饮食蛋白质的动脉动脉作用及其潜在的分子机制.
检查饮食蛋白质和特定氨基酸对人类和小鼠巨细胞功能和自细胞的影响.
确定减轻蛋白质诱导心血管疾病风险的潜在治疗点.

主要方法:

用小鼠进行的研究,以确定食蛋白和巨细胞MTORC1信号传递的动性作用.
对人类单细胞和巨细胞进行分析,以剖析MTORC1-自级联.
用小鼠模型中调制蛋白质和白含量的剂量依赖性研究.
评估单细胞/巨细胞功能障碍和动脉样硬化进展.

主要成果:

发现饮食中的蛋白质通过通过巨细胞MTORC1信号传递来抑制保护性自途径,从而起到异位性作用.
氨酸被确定为关键氨基酸,度超过特定值会触发致病信号.
这种氨酸的值效应被证实在小鼠模型中驱动动动脉硬化.
人类单细胞和巨细胞研究证实了动物模型的发现.

结论:

饮食中的白,在度超过关键值时,在心血管疾病中起病原作用.
巨细胞的MTORC1信号,由白激活,是这个过程的中心调解者.
选择性抑制巨细胞的白-MTOR信号传递,为心血管疾病提供了一个有前途的治疗策略.

关键词:

动脉样硬化是一种动脉样硬化.在 MTOR 中,我们可以使用 MTOR.自自是自的过程.饮食中的蛋白质饮食中的蛋白质氨酸 (leucine) 是一种蛋白质.巨细胞是一个巨细胞.

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