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[人主动脉正常及动脉粥样硬化内膜中的脂联素]

[Adiponectin in normal and atherosclerotic intima of human aorta].

作者信息

Tanyanskiy D A, Pigarevskii P V, Maltseva S V, Malashicheva A B, Docshin P M, Uspenskiy V E, Lizunov A V, Orlov S V, Maltseva O N, Ageeva E V, Denisenko A D

机构信息

Institute of Experimental Medicine, St. Petersburg, Russia.

Saint Petersburg State University, St. Petersburg, Russia.

出版信息

Arkh Patol. 2022;84(6):16-22. doi: 10.17116/patol20228406116.

Abstract

BACKGROUND

Adiponectin (AN) is a protein synthesized by adipocytes that has regulatory effects on lipid and lipoprotein metabolism, increases tissue sensitivity to insulin, and modulates endothelial functions and inflammatory response. However, its involvement in the processes of atherogenesis remains poorly understood.

OBJECTIVE

To determine the localization and sources of AN in atherosclerotic and normal human aortic intima.

MATERIAL AND METHODS

Immunohistochemical study was performed on sections of atherosclerotic and normal human aorta obtained during autopsy. Reverse transcription real-time PCR was performed using biopsies of para-aortic and abdominal adipose tissue, intima-media of the thoracic aorta, atherosclerotic plaques of the human carotid and femoral arteries, as well as on endothelial cells isolated from the human thoracic aorta. Transendothelial transport of AN was evaluated in a two-chamber model using a monolayer of human endothelial cell hybridoma EA.Hy926.

RESULTS

It has been established that AN is present in atherosclerotic but not in normal human aortic intima. At the same time, AN mRNA was not detected either in the intima media of the human aorta, nor in isolated endothelial cells of the aorta, nor in cells of atherosclerotic plaques of the carotid and femoral arteries. AN slowly penetrated the endothelial monolayer in vitro, but this transport was significantly enhanced by the action of tumor necrosis factor-alpha (TNFa).

CONCLUSION

Obtained data indicate that AN is present in atherosclerotic but not in normal aortic intima. We assume that AN is not synthesized by the cells of normal and atherosclerotic arterial walls, but permeates from the plasma. Transendothelial transport of AN, like many other plasma proteins, is activated during the development of atherosclerotic lesions, apparently under the action of pro-inflammatory cytokines, in particular, TNFα.

摘要

背景

脂联素(AN)是一种由脂肪细胞合成的蛋白质,对脂质和脂蛋白代谢具有调节作用,可增加组织对胰岛素的敏感性,并调节内皮功能和炎症反应。然而,其在动脉粥样硬化形成过程中的作用仍知之甚少。

目的

确定AN在人类动脉粥样硬化和正常主动脉内膜中的定位及来源。

材料与方法

对尸检时获取的人类动脉粥样硬化和正常主动脉切片进行免疫组织化学研究。使用主动脉旁和腹部脂肪组织活检标本、胸主动脉中膜、人类颈动脉和股动脉粥样硬化斑块以及从人类胸主动脉分离的内皮细胞进行逆转录实时聚合酶链反应。在双室模型中使用人内皮细胞杂交瘤EA.Hy926单层评估AN的跨内皮转运。

结果

已证实AN存在于人类动脉粥样硬化主动脉内膜中,而不存在于正常主动脉内膜中。同时,在人类主动脉中膜、分离的主动脉内皮细胞以及颈动脉和股动脉粥样硬化斑块细胞中均未检测到AN mRNA。在体外,AN缓慢穿透内皮单层,但肿瘤坏死因子-α(TNFα)的作用可显著增强这种转运。

结论

所得数据表明AN存在于动脉粥样硬化主动脉内膜中,而不存在于正常主动脉内膜中。我们推测AN并非由正常和动脉粥样硬化动脉壁细胞合成,而是从血浆中渗透而来。与许多其他血浆蛋白一样,AN的跨内皮转运在动脉粥样硬化病变发展过程中被激活,显然是在促炎细胞因子尤其是TNFα的作用下。

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