Plasma Lipid Profiling Identifies Biomarkers of Cerebral Microvascular Disease
Plasma Lipid Profiling Identifies Biomarkers of Cerebral Microvascular Disease
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DOI：
10.3389/fneur.2019.00950
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发表时间：
2019-08-29
影响因子：
3.4
通讯作者：
Hinman, Jason D.
中科院分区：
文献类型：
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作者：
Azizkhanian, Ida;Sheth, Sunil A.;Hinman, Jason D.
脑特异性鞘脂（SL）可以作为白质高信号（WMH）的有效生物标志物。在这里，我们研究 SL 作为一种新型液体生物标志物的功效，以识别反映慢性缺血的 WMH。到我们的卒中中心评估急性神经功能缺损的患者均参加了近期卒中高级血清分析 (ASPIRE) 研究。在这个由 202 名个体组成的队列中，58 名接受 MRI 且没有发生临床中风事件的患者被纳入本研究。在 MRI 时收集血浆样本，并通过 HPLC/串联质谱法进行目标 SL 分析。 T-2 FLAIR 成像评估 WMH，根据 Fazekas 评分 (FS) 方法进行评分并手动量化。最终鉴定出 22 种 SL，包括神经酰胺 (Cer) 和鞘磷脂 (SM) 种类。其中，两种鞘脂 SM 38:1 和 Cer 34:1 与高 FS 显着相关（分别为 r = 0.287，p = 0.029 和 r = 0.356，p = 0.006），并用于后续分析。 SM 38: 1（OR 1.129，95% CI 1.032, 1.236，p = 0.008）和 Cer 34:1（OR 1.118，95% CI 1.031, 1.212，p = 0.007），在回归分析中准确地区分 FS 0-2 与 2.5-6。综合血脂评分在 ROC 分析中表现出公平的辨别力（AUC = 0.729，p = 0.003），并使用留一分析进行交叉验证。大脑特异性 SL 的血浆水平可以作为亚急性白质疾病的有效生物标志物。
Brain-specific sphingolipids (SLs) may serve as effective biomarkers of white matter hyperintensities (WMH). Here, we investigate the efficacy of SLs as a novel fluid-based biomarker to identify WMH reflective of chronic ischemia. Patients presenting to our stroke center for evaluation of acute neurological deficits were enrolled in the Advanced Serum Profiling in Recent Stroke (ASPIRE) study. From this cohort of 202 individuals, 58 patients who underwent an MRI and did not have a clinical stroke event were included in this study. Plasma samples were collected at the time of MRI, and targeted SL profiling was performed by HPLC/tandem mass spectrometry. T-2 FLAIR imaging was evaluated for WMH and scored according to the Fazekas scoring (FS) method and manually quantified. Twenty two SLs were definitively identified, consisting of ceramide (Cer) and sphingomyelin (SM) species. Of these, two sphingolipids, SM 38:1 and Cer 34:1, significantly correlated with high FS (r = 0.287, p = 0.029, and r = 0.356, p = 0.006, respectively) and were used in subsequent analysis. SM 38: 1 (OR 1.129, 95% CI 1.032, 1.236, p = 0.008) and Cer 34:1 (OR 1.118, 95% CI 1.031, 1.212, p = 0.007), accurately differentiated between FS 0-2 vs. 2.5-6 in regression analysis. A combined lipid score demonstrated fair discrimination in ROC analysis (AUC = 0.729, p = 0.003) and was cross-validated using leave-one-out analysis. Plasma levels of brain-specific SLs may serve as effective biomarkers of subacute white matter disease.