Department of Neurology, School of Medicine, National Yang Ming University, Taipei, Taiwan.
Department of Neurology, Taipei Veterans General Hospital, No. 201, Section 2, Shih-Pai Road, Taipei, 112, Taiwan.
Transl Stroke Res. 2019 Jun;10(3):265-272. doi: 10.1007/s12975-018-0639-6. Epub 2018 Jun 25.
High phosphate is linked to vascular calcification and endothelial dysfunction; however, its relationship with cerebral small-vessel diseases (CSVDs) is still unknown. Study subjects were prospectively recruited from the community-based I-Lan Longitudinal Aging Study. CSVDs including lacunes, white matter hyperintensities (WMHs), and cerebral microbleeds were evaluated using 3T magnetic resonance images. Multivariate analyses were performed to study the associations between circulatory phosphate level and the presence of CSVDs. In vitro experiments included human brain microvascular endothelial cell (HBMEC) studies and western blotting. The present study included 186 subjects (age [mean ± standard deviation, range] 64.7 ± 8.6, 50-86.8 years; 93 men). Multivariate analysis revealed that circulatory phosphate levels > 3.925 mg/dL were associated with severe WMH with an odds ratio of 3.7 (95% confidence interval = 1.3-10.6) independent of age, sex, traditional vascular risk factors, total cholesterol, renal function, or circulatory calcium level. The in vitro study revealed a downregulation of tight junction protein (zona occludens-1, occludin, and claudin-5) expression in HBMECs after 48 h of treatment with high phosphate (2.5/5 mM). We are the first to report a relationship between circulatory phosphate and CSVDs. Our results suggest that high circulatory phosphate level might be a novel risk factor for CSVD, possibly by impairing BBB structures.
高磷与血管钙化和内皮功能障碍有关;然而,其与脑小血管疾病(CSVD)的关系尚不清楚。研究对象是从基于社区的宜兰纵向老龄化研究中前瞻性招募的。使用 3T 磁共振成像评估 CSVD 包括腔隙、白质高信号(WMHs)和脑微出血。进行多变量分析以研究循环磷酸盐水平与 CSVD 存在之间的关系。体外实验包括人脑微血管内皮细胞(HBMEC)研究和蛋白质印迹。本研究包括 186 名受试者(年龄[平均值±标准差,范围]64.7±8.6,50-86.8 岁;93 名男性)。多变量分析显示,循环磷酸盐水平>3.925mg/dL 与严重的 WMH 相关,优势比为 3.7(95%置信区间=1.3-10.6),独立于年龄、性别、传统血管危险因素、总胆固醇、肾功能或循环钙水平。体外研究显示,高磷(2.5/5mM)处理 48 小时后,HBMEC 中紧密连接蛋白(zonula occludens-1、occludin 和 claudin-5)的表达下调。我们是第一个报告循环磷酸盐与 CSVD 之间关系的人。我们的结果表明,高循环磷酸盐水平可能是 CSVD 的一个新的危险因素,可能通过损害 BBB 结构。
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