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[早期血管损伤的生物标志物与机制]

[Biomarkers and mechanisms of early vascular damage].

作者信息

Dobrynina L A, Gnedovskaya E V, Shabalina A A, Sergeeva A N, Kravchenko M A, Nikolaeva N S

机构信息

Research Center of Neurology, Moscow, Russia.

出版信息

Zh Nevrol Psikhiatr Im S S Korsakova. 2018;118(12. Vyp. 2):23-32. doi: 10.17116/jnevro201811812223.

Abstract

AIM

To assess the association of classic vascular risk factors, indicators of cerebral arteries wall damage and stress induction, and their role in early vascular and brain damage in middle age subjects without vascular events.

MATERIAL AND METHODS

87 patients were evaluated (49 women, 38 men, mean age 51.2±6.5). The following vascular risk factors were assessed: hypertension, diabetes, total cholesterol and low density lipoproteins levels, obesity and smoking. Patients underwent ultrasound of neck arteries, brain MRI and laboratory testing of blood parameters, probably associated with vascular wall damage: CRP, TNF-α, sICAM-1, sVCAM, HIF1-α, NO, VAP-1, VEGF-A, VEGF-C, sVEGF-R1, sVEGF-R2, TGF-β1, general antioxidant status.

RESULTS AND CONCLUSION

Mediating role of stress parameters in risk factors formation, initiation and maintenance of mechanisms of vascular damage was demonstrated. Hypercortisolemia suggested the association with age, atheromatosis, local inflammatory reactions via the TGF-β1-HIF-1-VEGF family, systemic inflammation response via CRP, and elevated epinephrine levels were associated with TNF-α-mediated systemic inflammation. The association of TNF-α and MRI signs of cerebral small vessel disease (SVD) in non-hypertensive patients may indicate that TNF-α-mediated inflammation and increased permeability of vessel wall is an independent cause and potential biomarker of early small vessel damage. Influence of hypertension on age-dependent SVD is probably maintained by local vascular wall damage mechanisms via the TGF-β1-HIF-1-VEGF family. However, hypertension heterogeneity and association of early cerebral vessels damage with various protective reactions require further clarification of the conditions for using these parameters as possible biomarkers of early SVD.

摘要

目的

评估经典血管危险因素、脑动脉壁损伤指标和应激诱导之间的关联,以及它们在无血管事件的中年受试者早期血管和脑损伤中的作用。

材料与方法

对87例患者进行了评估(49例女性,38例男性,平均年龄51.2±6.5岁)。评估了以下血管危险因素:高血压、糖尿病、总胆固醇和低密度脂蛋白水平、肥胖和吸烟。患者接受了颈部动脉超声、脑部MRI检查以及血液参数的实验室检测,这些参数可能与血管壁损伤有关:CRP、TNF-α、sICAM-1、sVCAM、HIF1-α、NO、VAP-1、VEGF-A、VEGF-C、sVEGF-R1、sVEGF-R2、TGF-β1、一般抗氧化状态。

结果与结论

证明了应激参数在危险因素形成、血管损伤机制启动和维持中的中介作用。高皮质醇血症提示与年龄、动脉粥样硬化、通过TGF-β1-HIF-1-VEGF家族的局部炎症反应相关,通过CRP的全身炎症反应,以及肾上腺素水平升高与TNF-α介导的全身炎症相关。非高血压患者中TNF-α与脑小血管病(SVD)的MRI征象之间的关联可能表明,TNF-α介导的炎症和血管壁通透性增加是早期小血管损伤的独立原因和潜在生物标志物。高血压对年龄依赖性SVD的影响可能是通过TGF-β1-HIF-1-VEGF家族的局部血管壁损伤机制维持的。然而,高血压的异质性以及早期脑血管损伤与各种保护反应的关联需要进一步阐明将这些参数用作早期SVD可能生物标志物的条件。

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