血管生成标志物的性别差异与人类大脑衰老轨迹有关。

IF 15.8 1区 医学 Q1 CELL BIOLOGY
Abel Torres-Espin, Hannah L. Radabaugh, Scott Treiman, Stephen S. Fitzsimons, Danielle Harvey, Austin Chou, Cutter A. Lindbergh, Kaitlin B. Casaletto, Lauren Goldberger, Adam M. Staffaroni, Pauline Maillard, Bruce L. Miller, Charles DeCarli, Jason D. Hinman, Adam R. Ferguson, Joel H. Kramer, Fanny M. Elahi
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引用次数: 0

摘要

血管生成异常可能会导致认知障碍的发生,并成为预防痴呆症的治疗目标。然而,大多数有关血管生成和认知障碍的研究都集中在模式生物上。为了检验血管生成与人类认知衰老的相关性,我们从深度表型纵向人类队列(n = 435;女性 = 207,年龄 = 74 ± 9)中收集了两个中心的样本,利用认知评估、生物样本、脑结构成像和临床数据,评估了循环血液中血管生成标记物与脑衰老轨迹的相关性。血液标记物包括参与血管生成和血管功能的配体,如碱性成纤维细胞生长因子(bFGF)、血管内皮生长因子家族成员(VEGFA、VEGFB 和 VEGFC)和胎盘生长因子(PlGF),以及它们的受体血管内皮生长因子受体 1(VEGFR1)和具有免疫球蛋白和 EGF 同源结构域 2 的酪氨酸激酶(Tie2)。机器学习和传统统计学揭示了血浆血管生成生长因子与大脑衰老结果(包括执行功能和灰质萎缩)之间的性别双态关联。具体来说,血管生成标志物与年轻女性(非男性)较高的执行功能和较少的脑萎缩有关,这种关联的方向性在 75 岁左右发生逆转。众所周知,bFGF 对多种类型的细胞具有多向效应,其浓度越高,预测女性和男性的认知轨迹越有利。来自一个多中心数据集(MarkVCID;n = 80;女性 = 30,年龄 = 73 ± 9)的独立样本被用来从外部验证这些发现。总之,这项分析证明了血管生成与人类大脑衰老的关系,对血管性认知障碍和痴呆症具有潜在的治疗意义。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Sexually dimorphic differences in angiogenesis markers are associated with brain aging trajectories in humans
Aberrant angiogenesis could contribute to the development of cognitive impairment and represent a therapeutic target for preventing dementia. However, most studies addressing angiogenesis and cognitive impairment focus on model organisms. To test the relevance of angiogenesis to human cognitive aging, we evaluated associations of circulating blood markers of angiogenesis with brain aging trajectories in a pooled two-center sample from deeply phenotyped longitudinal human cohorts (n = 435; female = 207, age = 74 ± 9) using cognitive assessments, biospecimens, structural brain imaging, and clinical data. Blood markers included ligands involved in angiogenesis and vascular function such as basic fibroblast growth factor (bFGF), members of the vascular endothelial growth factor family (VEGFA, VEGFB, and VEGFC), and placental growth factor (PlGF), in addition to their receptors VEGF receptor 1 (VEGFR1) and tyrosine kinase with immunoglobulin and EGF homology domain 2 (Tie2). Machine learning and traditional statistics revealed sexually dimorphic associations of plasma angiogenic growth factors with brain aging outcomes, including executive function and gray matter atrophy. Specifically, markers of angiogenesis were associated with higher executive function and less brain atrophy in younger women (not men), a directionality of association that reversed around age 75. Higher concentrations of bFGF, known for pleiotropic effects on multiple cell types, predicted favorable cognitive trajectories in both women and men. An independent sample from a multicenter dataset (MarkVCID; n = 80; female = 30, age = 73 ± 9) was used to externally validate these findings. In conclusion, this analysis demonstrates the association of angiogenesis to human brain aging, with potential therapeutic implications for vascular cognitive impairment and dementia.
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来源期刊
Science Translational Medicine
Science Translational Medicine CELL BIOLOGY-MEDICINE, RESEARCH & EXPERIMENTAL
CiteScore
26.70
自引率
1.20%
发文量
309
审稿时长
1.7 months
期刊介绍: Science Translational Medicine is an online journal that focuses on publishing research at the intersection of science, engineering, and medicine. The goal of the journal is to promote human health by providing a platform for researchers from various disciplines to communicate their latest advancements in biomedical, translational, and clinical research. The journal aims to address the slow translation of scientific knowledge into effective treatments and health measures. It publishes articles that fill the knowledge gaps between preclinical research and medical applications, with a focus on accelerating the translation of knowledge into new ways of preventing, diagnosing, and treating human diseases. The scope of Science Translational Medicine includes various areas such as cardiovascular disease, immunology/vaccines, metabolism/diabetes/obesity, neuroscience/neurology/psychiatry, cancer, infectious diseases, policy, behavior, bioengineering, chemical genomics/drug discovery, imaging, applied physical sciences, medical nanotechnology, drug delivery, biomarkers, gene therapy/regenerative medicine, toxicology and pharmacokinetics, data mining, cell culture, animal and human studies, medical informatics, and other interdisciplinary approaches to medicine. The target audience of the journal includes researchers and management in academia, government, and the biotechnology and pharmaceutical industries. It is also relevant to physician scientists, regulators, policy makers, investors, business developers, and funding agencies.
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