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阻塞性睡眠呼吸暂停患者卒中前后新型血管和炎症生物标志物的血浆浓度变化。

Changes in plasma concentrations of novel vascular and inflammatory biomarkers in obstructive sleep apnea patients pre- and post-stroke.

机构信息

Department of Biochemistry and Molecular Biology, Mayo Clinic Florida, Jacksonville, FL, USA.

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA.

出版信息

Sleep Med. 2024 Jul;119:518-525. doi: 10.1016/j.sleep.2024.05.034. Epub 2024 May 17.

Abstract

BACKGROUND

Obstructive sleep apnea (OSA) is increasingly recognized as a common condition in the general population and causes significant OSA-associated morbidities including cardiovascular and cerebrovascular events such as cerebral small vessel disease (CSVD) and stroke.

METHODS

In this study, using sensitive ELISA immunoassays, we measured subset of endothelial/vascular and inflammatory biomarkers as well as neurofilament light chain (NfL), a sensitive marker for neuroaxonal injury, using plasma from OSA patients post-stroke (Acute Cerebral Infarction (ACI), N = 26) to determine their usefulness as potential prognostic markers in disease progression.

RESULTS

Our results showed significantly increased plasma TNFα and NfL concentrations and decreased concentrations of platelet derived growth factor (PDGF-AA) in post-stroke OSA patients with more severe white matter hyperintensities (WMHs). And after separating the patients based on sex, compared to females, male post-stroke OSA patients with severe WMHs have increased circulating levels of inflammatory chemokine CXCL10 and cytokine Interleukin-10 (IL-10) and significantly decreased levels of Angiopoietin-1 (Ang-1) an important protein responsible for endothelial/vascular integrity functions. Importantly, in a subset of newly diagnosed OSA patients (without prior history of stroke), significantly increased plasma CXCL10 levels and decreased plasma Ang-1 levels were also readily observed when compared to healthy controls, indicating possible altered endothelial integrity and ongoing vascular inflammation in these newly diagnosed OSA patients.

CONCLUSIONS

In summary, our study has identified a novel set of plasma biomarkers including PDGF-AA, CXCL10 and Ang-1 for their potential prognostic value for disease outcomes pre- and post-stroke in OSA patients and use as surrogate markers to measure efficacy of treatment modalities.

摘要

背景

阻塞性睡眠呼吸暂停(OSA)在普通人群中越来越被认为是一种常见疾病,会导致与 OSA 相关的多种疾病,包括心血管和脑血管事件,如脑小血管病(CSVD)和中风。

方法

在这项研究中,我们使用敏感的 ELISA 免疫分析,测量了一组内皮/血管和炎症生物标志物,以及神经丝轻链(NfL),一种神经轴突损伤的敏感标志物,使用 OSA 患者中风后的血浆(急性脑梗死(ACI),N=26),以确定它们作为疾病进展中潜在预后标志物的有用性。

结果

我们的结果表明,在 OSA 后中风患者中,TNFα 和 NfL 浓度显著升高,血小板衍生生长因子(PDGF-AA)浓度降低,且在白质高信号(WMH)更严重的患者中。并且,根据性别将患者分开后,与女性相比,严重 WMH 的男性 OSA 后中风患者循环中促炎趋化因子 CXCL10 和细胞因子白细胞介素 10(IL-10)水平升高,而血管生成素 1(Ang-1)水平显著降低,Ang-1 是一种负责内皮/血管完整性功能的重要蛋白。重要的是,在一组新诊断的 OSA 患者(无中风既往史)中,与健康对照组相比,也很容易观察到 CXCL10 水平显著升高,Ang-1 水平显著降低,表明这些新诊断的 OSA 患者可能存在内皮完整性改变和持续的血管炎症。

结论

总之,我们的研究确定了一组新的血浆生物标志物,包括 PDGF-AA、CXCL10 和 Ang-1,它们对 OSA 患者中风前后的疾病预后具有潜在的预测价值,并可作为衡量治疗效果的替代标志物。

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