早期间歇性高脂血症会改变组织巨细胞,导致动脉样硬化
Minoru Takaoka1, Xiaohui Zhao1, Hwee Ying Lim2,3
1Department of Medicine, Section of CardioRespiratory Medicine, University of Cambridge, Heart and Lung Research Institute, Cambridge, UK.
Nature
|September 4, 2024
概括
早期高胆固醇暴露会通过改变动脉巨细胞加速动脉样硬化,即使累积的LDL-C水平相似. 对于预防心血管疾病而言,最佳的超脂血控制至关重要.
科学领域:
- 心血管研究
- 免疫学
- 代谢疾病
背景情况:
- 超脂血是动脉样硬化心血管疾病 (ASCVD) 的关键危险因素.
- 早期和波动性的低密度脂蛋白胆固醇 (LDL- C) 独立增加ASCVD风险.
- 早期高脂血症与加速的ASCVD相关的机制尚未完全理解.
研究的目的:
- 研究早期间歇性高胆固醇饮食对动脉样硬化的影响.
- 阐明动脉巨和特定生物途径在饮食引起的ASCVD中的作用.
- 为了将早期的胆固醇暴露与人类中期的动脉样硬化相关联.
主要方法:
- 给小鼠进行间歇性高胆固醇西式饮食 (WD) 或连续性WD.
- 对动脉巨细胞群的分析,基因表达和动脉保护途径.
- 长度人类研究 (年轻芬兰人研究) 评估早期的胆固醇暴露和动脉斑块的发展.
主要成果:
- 早期间歇性WD食在小鼠中加速动脉样硬化,尽管与连续性WD相比,LDL- C的累积水平相似.
- 在早期暴露的小鼠中观察到类似常存性动脉巨细胞的数量和表型发生变化.
- 鉴定出LYVE1+巨细胞具有动脉动脉保护性,其活性组织途径与加速动脉样硬化有关.
- 在人类中,早期的胆固醇暴露与成年期中枢动脉斑块发生率和大小有显著的相关性.
结论:
- 早期间歇性胆固醇暴露是加速动脉样硬化的重要决定因素.
- 动脉巨的改变和特定的细胞通路是关键的机制.
- 在生命早期控制高脂血是预防ASCVD的关键.
- 这些发现为制定针对ASCVD的治疗策略提供了洞察力.
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