由血小板相互作用和氧化应激信号定义的单细胞是HIV相关动脉样硬化的基础
Ruoqiao H Wang1,2, Zachary D Boodoo2, Karli R Sutton2
1Department of Biomedical Genetics and Genomics University of Rochester School of Medicine and Dentistry Rochester NY.
Journal of the American Heart Association
|March 13, 2026
概括
艾滋病毒感染者的明显单细胞子集有助于血管炎症和内皮功能障碍,可能加速动脉样硬化. 血小板单细胞复合体和激活的CD14+单细胞驱动这些过程,即使没有传统的风险因素.
科学领域:
- 免疫学 免疫学 免疫学
- 心血管研究研究心血管研究
- 病毒学 病毒学
背景情况:
- 单细胞是动脉样硬化中的关键参与者,迁移到炎症的内皮并成为带有脂质的巨细胞.
- 艾滋病毒感染者 (PLWH) 由于慢性炎症而面临动脉样硬化风险增加,但特定单细胞子集的作用尚未完全理解.
- 这项研究调查了不同单细胞群对早期艾滋病毒相关动脉样硬化的血管病理的贡献.
研究的目的:
- 在艾滋病毒和动脉样硬化背景下,识别和描述涉及血管病理的特定单细胞子集.
- 阐明这些单细胞子集有助于内皮功能障碍和免疫调节障碍的机制.
- 了解血小板-单细胞相互作用如何影响单细胞功能和PLWH中的血管炎症.
主要方法:
- 单细胞RNA测序123,965个循环的单细胞和血微粒蛋白质组来自32个被HIV和动脉样硬化状态分层的个体.
- 监督学习以识别集群和疾病特定的特征.
- 使用血小板单细胞共同培养,RT-qPCR,大量RNA测序,流细胞计和ELISA进行验证.
主要成果:
- 确定了七个单细胞群,其中包括形成血小板-单细胞复合体 (PMCs) 的子集.
- 血小板单细胞共同培养显示了与炎症,脂质代谢,氧化应激和内皮粘附相关的基因的血小板驱动的上调.
- 由PMC衍生的巨细胞促进了内皮细胞转化为介质酶的转变,并分泌了促炎性细胞因子 (IL-6,CCL2) 和益纤维素因子 (TGF-β,IL-10). CD14+单细胞表现出增强的氧化应激信号 (ROS-NRF2通路活性).
结论:
- 两个不同的单细胞群独立地促进了PLWH中的血管免疫失调.
- 由PMC衍生的巨细胞促进内皮功能障碍,并采用益纤维化特征,而CD14+单细胞则表现出较高的氧化应激反应.
- 这些机制共同加快了PLWH的动脉样硬化发展,而不管传统的心血管风险因素.
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