背景:细胞外基质(ECM)在心肌梗死(MI)后发生实质性改变,包括白细胞亚型的入侵。尽管在心外膜层面完全重新开放,梗死心肌内灌注不足,称为微血管阻塞(MVO),发生并对心室重构产生负面影响。在这项研究中,使用形态计量学分析描述了MVO区域处的ECM组成。
方法:雌性猪(n=10)通过短暂的90分钟冠状动脉闭塞,然后再灌注7天诱导MI。在安乐死之前,冠状动脉内输注硫黄素S。在梗塞心肌内,分离显示MVO(硫黄素-S-)或不显示MVO(硫黄素-S+)的区域并染色以形态计量学比较ECM组成。
结果:如细胞通过ECM侵入所反映的,具有MVO的区域显示中性粒细胞和淋巴细胞的增大,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。的确,那些具有宏观MVO的区域显示出比没有MVO的区域更低的毛细管密度。最后,总胶原蛋白的延伸显著减少,I型,但不是III型,胶原蛋白,层粘连蛋白,与没有微血管损伤的区域相比,在显示MVO的区域中注意到纤连蛋白和多糖的增加。
结论:与那些没有微血管灌注不足的区域相比,在从母猪分离的MVO梗死区域的ECM组成显示出较高的炎症浸润和多糖的存在以及减少的微血管数量和胶原含量。这些特征可能是患有广泛MVO的MI患者不良心室重塑发展的基础。
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.