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脂肪因子作为肥胖受试者动脉粥样硬化血栓形成的危险因素:与止血标志物及颈总动脉壁厚度的关联

Adipokines as atherothrombotic risk factors in obese subjects: Associations with haemostatic markers and common carotid wall thickness.

作者信息

Csongrádi É, Káplár M, Nagy B, Koch C A, Juhász A, Bajnok L, Varga Z, Seres I, Karányi Z, Magyar M T, Oláh L, Facskó A, Kappelmayer J, Paragh G

机构信息

Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary; Department of Medicine, University of Mississippi Medical Center, Jackson, MS, United States.

Department of Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.

出版信息

Nutr Metab Cardiovasc Dis. 2017 Jun;27(6):571-580. doi: 10.1016/j.numecd.2017.02.007. Epub 2017 Mar 8.

Abstract

BACKGROUND AND AIMS

Some crucial associations between obesity-related altered adipokine levels and the main factors of atherosclerotic, atherothrombotic processes are not fully known. We analysed the relationships of classic adipokines, namely leptin, resistin, adiponectin, tumour necrosis factor-alpha (TNF-α), interleukin 6 (IL-6) with the markers of platelet activation, including mean platelet volume (MPV), platelet surface/soluble P-selectin, platelet-derived microparticles (PMPs), the parameters of coagulation abnormalities and common carotid intima-media thickness (IMT) in obese patients with or without atherosclerotic comorbidities in comparison to age- and sex-matched controls.

METHODS AND RESULTS

We enrolled 154 obese individuals, including 98 suffering from atherosclerotic concomitant conditions, 56 free of atherosclerotic comorbidities and 62 healthy controls. Plasma levels of leptin, resistin, adiponectin, TNF-α, IL-6, soluble P-selectin, and plasminogen activator inhibitor-1 antigen (PAI-1 ag) were analysed by ELISA. Platelet surface P-selectin and PMPs were measured by flow cytometry. IMT was detected by ultrasonography. Adipokines were closely associated with markers of platelet hyperactivity, hypercoagulability, hypofibrinolysis and IMT. Significant independent associations were found between leptin and platelet count (p < 0.0001), MPV (p = 0.019), PMPs (p < 0.0001), fibrinogen (p = 0.001), factor VIII (FVIII) activity (p = 0.035); adiponectin and PAI-1 ag (p = 0.035); resistin and soluble P-selectin (p = 0.002); TNF-α and PAI-1 ag (p < 0.0001); and IL-6 and fibrinogen (p = 0.011). Finally, leptin (p = 0.0005), adiponectin (p = 0.019), IL-6 (p = 0.001), MPV (p = 0.0003), PMP (p = 0.008), and FVIII activity (p = 0.043) were independent predictors of IMT.

CONCLUSION

Overall, we suggest that in obese subjects altered adipokine levels play a key role in common carotid atherosclerosis both directly and through haemostatic parameters.

摘要

背景与目的

肥胖相关的脂肪因子水平改变与动脉粥样硬化、动脉粥样血栓形成过程的主要因素之间的一些关键关联尚未完全明确。我们分析了经典脂肪因子,即瘦素、抵抗素、脂联素、肿瘤坏死因子-α(TNF-α)、白细胞介素6(IL-6)与血小板活化标志物之间的关系,这些标志物包括平均血小板体积(MPV)、血小板表面/可溶性P-选择素、血小板衍生微粒(PMPs)、凝血异常参数以及普通颈动脉内膜中层厚度(IMT),研究对象为有或无动脉粥样硬化合并症的肥胖患者,并与年龄和性别匹配的对照组进行比较。

方法与结果

我们纳入了154名肥胖个体,其中98名患有动脉粥样硬化合并症,56名无动脉粥样硬化合并症,以及62名健康对照者。通过酶联免疫吸附测定法(ELISA)分析瘦素、抵抗素、脂联素、TNF-α、IL-6、可溶性P-选择素和纤溶酶原激活物抑制剂-1抗原(PAI-1 ag)的血浆水平。通过流式细胞术测量血小板表面P-选择素和PMPs。通过超声检查检测IMT。脂肪因子与血小板高活性、高凝性、低纤溶活性和IMT标志物密切相关。发现瘦素与血小板计数(p < 0.0001)、MPV(p = 0.019)、PMPs(p < 0.0001)、纤维蛋白原(p = 0.001)、因子VIII(FVIII)活性(p = 0.035)之间存在显著的独立关联;脂联素与PAI-1 ag(p = 0.035)之间存在显著的独立关联;抵抗素与可溶性P-选择素(p = 0.002)之间存在显著的独立关联;TNF-α与PAI-1 ag(p < 0.0001)之间存在显著的独立关联;IL-6与纤维蛋白原(p = 0.011)之间存在显著的独立关联。最后,瘦素(p = 0.0005)、脂联素(p = 0.019)、IL-6(p = 0.001)、MPV(p = 0.0003)、PMP(p = 0.008)和FVIII活性(p = 0.043)是IMT的独立预测因子。

结论

总体而言,我们认为在肥胖受试者中,改变的脂肪因子水平在普通颈动脉动脉粥样硬化中直接以及通过止血参数发挥关键作用。

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