通过三维大动脉几何学确定早期血管衰老:遗传决定因素和临床后果
Cameron Beeche1,2, Bingxin Zhao3, Hamed Tavolinejad4,2
1Department of Bioengineering, University of Pennsylvania, Philadelphia. (C.B., J.K.).
Circulation
|July 17, 2025
概括
通过大动脉血管年龄指数 (AVAI) 量化的早期大动脉衰老与不良心血管结果和疾病有关. 这种指数具有强烈的遗传基础,并可能对心房动和大动脉动脉瘤等疾病产生因果影响.
科学领域:
- 心血管医学
- 遗传学
- 医学成像
背景情况:
- 血管衰老涉及结构和几何重塑,有些人表现出超正常的衰老,而另一些人则表现出与不良结果相关的早期衰老.
- 大动脉表现出与年龄相关的突出变化,但底层的生物机制,遗传结构和与心血管健康的联系尚未完全理解.
研究的目的:
- 使用3D成像数据开发特定性别的模型来量化大动脉年龄.
- 评估大动脉年龄与心血管结构和功能之间的关联.
- 研究大动脉衰老与心血管疾病的遗传结构和因果关系.
主要方法:
- 使用 UK Biobank 和 Penn Medicine BioBank 的大动脉成像数据的卷积神经网络辅助的3D细分开发了性别特定的模型.
- 根据几何表型计算出大动脉血管年龄指数 (AVAI).
- 通过回归评估与心血管特征的关联,通过GWAS检查遗传结构,并使用孟德尔随机化推断因果关系.
主要成果:
- AVAI与左心室质量,壁厚度和左心室体积的增加有显著的关联.
- AVAI显示出高遗传性 (40. 24%) 与54个已识别的遗传位点,包括与FBN1和ELN1基因的关联.
- 孟德尔的随机化支持AVAI与心房动,血管痴呆,大动脉动脉瘤和大动脉解剖之间的因果关系.
结论:
- 早期的大动脉衰老与不良的心脏重塑和主要心血管疾病有显著关联.
- 大动脉血管年龄指数 (AVAI) 具有多基因和高度可遗传的遗传结构.
- AVAI与心血管疾病之间存在因果关系,包括心房动,血管痴呆症,大动脉动脉瘤和大动脉解剖.
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