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基质金属蛋白酶及其组织抑制剂作为细胞外基质重塑中主动脉瘤和主动脉夹层发展的指标。

Matrix metalloproteinases and their tissue inhibitors as indicators of aortic aneurysm and dissection development in extracellular matrix remodeling.

作者信息

Irqsusi Marc, Rodepeter Fiona R, Günther Madeline, Kirschbaum Andreas, Vogt Sebastian

机构信息

Department of Heart Surgery, Universitätsklinikum Marburg and Gießen GmbH, Marburg 35043, Hesse, Germany.

Institute of Pathology, Philipps-University Marburg, Marburg 35043, Hesse, Germany.

出版信息

World J Exp Med. 2025 Jun 20;15(2):100166. doi: 10.5493/wjem.v15.i2.100166.

Abstract

Aneurysms and dissections represent some of the most serious cardiovascular diseases. The prevailing theory posits that mechanical overloading of the vessel wall is the underlying cause. Inspired by Barkhordarian , the authors present matrix metalloproteinases (MMPs) and their inhibitors in immunohistological analyses as contributing factors in the pathophysiology of aortic aneurysms (AA). Data analysis of MMP-1, MMP-9, tissue inhibitors of metalloproteinases (TIMPs), including TIMP-1 and TIMP-2 expression reveals a varied distribution between the adventitia and media and a non-uniform expression of the investigated markers. These elements, as key components of the extracellular matrix (ECM), indicate that the formation of AA is not solely driven by endoluminal pressure loading of the aortic wall. Instead, degenerative processes within ECM elements contribute significantly. Importantly, AA do not necessarily imply dissection. Tissue destruction, allowing blood flow entry, arises from reduced oxygen supply to the media, primarily due to incomplete capillarization or neocapillarization.

摘要

动脉瘤和夹层是一些最严重的心血管疾病。目前的理论认为血管壁的机械过载是根本原因。受巴克霍达里安的启发,作者在免疫组织学分析中提出基质金属蛋白酶(MMPs)及其抑制剂是主动脉瘤(AA)病理生理学中的促成因素。对MMP-1、MMP-9、金属蛋白酶组织抑制剂(TIMPs)(包括TIMP-1和TIMP-2表达)的数据分析显示,外膜和中膜之间分布各异,且所研究标志物的表达并不均匀。这些作为细胞外基质(ECM)关键成分的因素表明,AA的形成并非仅由主动脉壁的腔内压力负荷驱动。相反,ECM成分内的退行性过程起了重要作用。重要的是,AA不一定意味着夹层。组织破坏使得血流进入,这主要是由于向中膜的氧气供应减少,主要原因是毛细血管化不完全或新生血管形成。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2140/12019616/20180f4e2024/100166-g001.jpg

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