Department of Neurosurgery, National Clinical Research Center of Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China.
Department of Neurosurgery, National Clinical Research Center of Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China; Research Center for Cerebrovascular Disease, Central South University, Changsha, 410008, China.
Neurotherapeutics. 2024 Sep;21(5):e00428. doi: 10.1016/j.neurot.2024.e00428. Epub 2024 Aug 3.
Intracranial aneurysm (IA) is the most prevalent type of cerebral vascular disease causing life-threatening subarachnoid hemorrhages (SAH). A long-term vascular structure remodeling is considered as the main pathophysiological feature of IAs. However, the causal factors triggering the pathophysiological process are not clear. Recently, the abnormalities of peripheral circulating proteins and metabolites have been found in IAs patients and associated with the ruptures. We comprehensively investigated the potential causal relationship between blood metabolites and proteins and IAs using the mendelian randomization (MR) analysis. We applied two-sample MR to explore the potential causal association between peripheral circulating metabolites (191 blood metabolites) and proteins (1398 proteins) and IAs using data from the FinnGen study and the GWAS datasets published by Bakker et al. We identified palmitoylcarnitine, stearoylcarnitine and 2-tetradecenoylcarnitine as causal contributors of IAs and ruptures. Further two-step mediation MR analysis suggested that hypertension as one of the contributors of IAs and ruptures mediated the causal relationship between palmitoylcarnitine, stearoylcarnitine and 2-tetradecenoylcarnitine and IAs. Together, our study demonstrates that blood metabolic palmitoylcarnitine, stearoylcarnitine and 2-tetradecenoylcarnitine are causally linked to the formation and rupture of IAs. Hypertension partially mediates the causal effects.
颅内动脉瘤（IA）是最常见的脑血管疾病类型，可导致危及生命的蛛网膜下腔出血（SAH）。长期的血管结构重塑被认为是 IAs 的主要病理生理特征。然而，引发病理生理过程的因果因素尚不清楚。最近，IA 患者的外周循环蛋白和代谢物异常已被发现，并与破裂有关。我们使用孟德尔随机化（MR）分析全面研究了血液代谢物和蛋白质与 IAs 之间的潜在因果关系。我们应用两样本 MR 分析，使用 FinnGen 研究的数据和 Bakker 等人发表的 GWAS 数据集，探讨了外周循环代谢物（191 种血液代谢物）和蛋白质（1398 种蛋白质）与 IAs 之间的潜在因果关联。我们确定棕榈酰肉碱、硬脂酰肉碱和 2-十四烯酰肉碱是 IAs 和破裂的因果贡献者。进一步的两步中介 MR 分析表明，高血压作为 IAs 和破裂的一个贡献者，介导了棕榈酰肉碱、硬脂酰肉碱和 2-十四烯酰肉碱与 IAs 之间的因果关系。总之，我们的研究表明，血液代谢物棕榈酰肉碱、硬脂酰肉碱和 2-十四烯酰肉碱与 IAs 的形成和破裂有因果关系。高血压部分介导了因果效应。
