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人腹主动脉瘤周围血管周围脂肪组织中的炎症细胞、神经酰胺和蛋白酶表达。

Inflammatory cells, ceramides, and expression of proteases in perivascular adipose tissue adjacent to human abdominal aortic aneurysms.

作者信息

Folkesson Maggie, Vorkapic Emina, Gulbins Erich, Japtok Lukasz, Kleuser Burkhard, Welander Martin, Länne Toste, Wågsäter Dick

机构信息

Division of Drug Research, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.

Department of Molecular Biology, University of Duisburg-Essen, Essen, Germany; Department of Surgery, University of Cincinnati, Cincinnati, Ohio.

出版信息

J Vasc Surg. 2017 Apr;65(4):1171-1179.e1. doi: 10.1016/j.jvs.2015.12.056. Epub 2016 Mar 6.

Abstract

BACKGROUND

Abdominal aortic aneurysm (AAA) is a deadly irreversible weakening and distension of the abdominal aortic wall. The pathogenesis of AAA remains poorly understood. Investigation into the physical and molecular characteristics of perivascular adipose tissue (PVAT) adjacent to AAA has not been done before and is the purpose of this study.

METHODS AND RESULTS

Human aortae, periaortic PVAT, and fat surrounding peripheral arteries were collected from patients undergoing elective surgical repair of AAA. Control aortas were obtained from recently deceased healthy organ donors with no known arterial disease. Aorta and PVAT was found in AAA to larger extent compared with control aortas. Immunohistochemistry revealed neutrophils, macrophages, mast cells, and T-cells surrounding necrotic adipocytes. Gene expression analysis showed that neutrophils, mast cells, and T-cells were found to be increased in PVAT compared with AAA as well as cathepsin K and S. The concentration of ceramides in PVAT was determined using mass spectrometry and correlated with content of T-cells in the PVAT.

CONCLUSIONS

Our results suggest a role for abnormal necrotic, inflamed, proteolytic adipose tissue to the adjacent aneurysmal aortic wall in ongoing vascular damage.

摘要

背景

腹主动脉瘤(AAA)是腹主动脉壁致命的、不可逆的薄弱和扩张。AAA的发病机制仍知之甚少。此前尚未对AAA周围血管周围脂肪组织(PVAT)的物理和分子特征进行研究,本研究旨在进行此项研究。

方法与结果

从接受择期AAA手术修复的患者身上采集人主动脉、主动脉周围PVAT和外周动脉周围脂肪。对照主动脉取自近期死亡的无已知动脉疾病的健康器官捐献者。与对照主动脉相比,AAA中的主动脉和PVAT范围更大。免疫组织化学显示坏死脂肪细胞周围有中性粒细胞、巨噬细胞、肥大细胞和T细胞。基因表达分析表明,与AAA相比,PVAT中的中性粒细胞、肥大细胞和T细胞以及组织蛋白酶K和S增加。使用质谱法测定PVAT中神经酰胺的浓度,并与PVAT中T细胞的含量相关联。

结论

我们的结果表明,异常坏死、炎症、蛋白水解的脂肪组织对相邻的动脉瘤性主动脉壁在持续的血管损伤中起作用。

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