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再灌注心肌梗死后微血管阻塞区细胞外基质的变化:形态计量学研究。

Changes in the extracellular matrix at microvascular obstruction area after reperfused myocardial infarction: A morphometric study.

机构信息

Department of Pathology, Universidad de Valencia, Valencia, Spain.

INCLIVA Health Research Institute, Valencia, Spain.

出版信息

Ann Anat. 2023 Oct;250:152138. doi: 10.1016/j.aanat.2023.152138. Epub 2023 Jul 26.

Abstract

BACKGROUND

Extracellular matrix (ECM) suffers substantial alterations after myocardial infarction (MI), including the invasion of leukocyte subtypes. Despite a complete reopening at epicardial level, hypoperfusion within the infarcted myocardium, known as microvascular obstruction (MVO), occurs and exerts a negative impact on ventricular remodeling. In this study, ECM composition at MVO regions was described using a morphometric analysis.

METHODS

MI was induced in female swine (n = 10) by transitory 90-minute coronary occlusion followed by seven days of reperfusion. Prior to euthanasia, intracoronary thioflavin-S was infused. Within the infarcted myocardium, regions displaying MVO (thioflavin-S-) or no MVO (thioflavin-S+) were isolated and stained to morphometrically compare ECM composition.

RESULTS

As reflected by cell invasion through ECM, areas with MVO displayed an enlarged presence of neutrophils and lymphocytes, whilst no differences in the amount of macrophages and myofibroblasts were detected compared to infarcted myocardium without MVO. Indeed, those regions with macroscopic MVO showed lower capillary density than areas without MVO. Lastly, a significant reduction in the extension of total collagen, type I, but not type III, collagen, laminin, and fibronectin together with an augmentation of polysaccharides were noted in areas showing MVO compared to those without microvascular injury.

CONCLUSIONS

ECM composition in infarcted regions with MVO isolated from female swine displays a higher presence of inflammatory infiltrate and polysaccharides as well as reduced number of microvessels and collagen content compared to those areas without microvascular hypoperfusion. These characteristics might underlie the development of adverse ventricular remodeling in MI patients with extensive MVO.

摘要

背景

心肌梗死后(MI)细胞外基质(ECM)会发生实质性改变,包括白细胞亚型的浸润。尽管心外膜水平完全再通,但梗死心肌内仍存在灌注不足,即微血管阻塞(MVO),这对心室重构产生负面影响。在这项研究中,我们使用形态计量学分析描述了 MVO 区域的 ECM 组成。

方法

通过短暂的 90 分钟冠状动脉闭塞后再灌注,在雌性猪(n=10)中诱导 MI。在安乐死前,经冠状动脉内注射硫代黄素-S。在梗死心肌内,分离并染色显示 MVO(硫代黄素-S-)或无 MVO(硫代黄素-S+)的区域,以形态计量学比较 ECM 组成。

结果

反映 ECM 中细胞浸润的情况,MVO 区域表现出更多的中性粒细胞和淋巴细胞浸润,而与无 MVO 的梗死心肌相比,巨噬细胞和肌成纤维细胞的数量没有差异。实际上,那些有宏观 MVO 的区域的毛细血管密度低于无 MVO 的区域。最后,与无微血管损伤区域相比,MVO 区域的总胶原、I 型胶原(但不是 III 型胶原)、层粘连蛋白和纤维连接蛋白的延伸明显减少,而多糖的含量增加。

结论

与无微血管灌注正常的梗死区域相比,从雌性猪分离出的 MVO 梗死区域的 ECM 组成表现出更高的炎症浸润和多糖含量,以及更少的微血管和胶原含量。这些特征可能是 MI 患者广泛 MVO 后发生不良心室重构的基础。

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