Kovanen P T, Kaartinen M, Paavonen T
Wihuri Research Institute, Helsinki, Finland.
Circulation. 1995 Sep 1;92(5):1084-8. doi: 10.1161/01.cir.92.5.1084.
Erosion and rupture of coronary atheromas are the events preceding the vast majority of acute coronary syndromes. The shoulder regions of atheromas, the sites at which erosion or rupture is most likely to occur, are the sites at which mast cells accumulate. These cells are filled with neutral proteases capable of triggering extracellular matrix degradation via activation of matrix metalloproteinases. To obtain more direct evidence for the participation of mast cells in the acute coronary syndromes, we quantified the numbers of mast cells at eroded or ruptured sites of coronary atheromas in patients who died of myocardial infarction.
In specimens of coronary arteries from 20 patients who had died of acute myocardial infarction, the site of atheromatous erosion or rupture was identified. The specimens were stained with monoclonal antibodies against the two major proteases of mast cells, tryptase and chymase, and against macrophages, T lymphocytes, and smooth muscle cells. At the immediate site of erosion or rupture, mast cells amounted to 6% of all nucleated cells, in the adjacent atheromatous area to 1%, and in the unaffected intimal area to 0.1%. The proportions of these mast cells that were activated, ie, had been stimulated to degranulate and release some of their tryptase and chymase contents, were 86% at the site of erosion or rupture, 63% in the adjacent atheromatous area, and 27% in the unaffected intima. At the site of erosion or rupture, the numbers of macrophages and T lymphocytes were also increased, but the number of smooth muscle cells was decreased.
The accumulation of activated mast cells (200-fold more than in the unaffected coronary intima) at the site of atheromatous erosion or rupture suggests that in thrombotic coronary occlusion the role played by mast cells is significant.
冠状动脉粥样硬化斑块的侵蚀和破裂是绝大多数急性冠状动脉综合征之前发生的事件。粥样硬化斑块的肩部区域是最容易发生侵蚀或破裂的部位，也是肥大细胞聚集的部位。这些细胞充满了中性蛋白酶，能够通过激活基质金属蛋白酶来触发细胞外基质降解。为了获得肥大细胞参与急性冠状动脉综合征的更直接证据，我们对死于心肌梗死患者的冠状动脉粥样硬化斑块侵蚀或破裂部位的肥大细胞数量进行了量化。
在20例死于急性心肌梗死患者的冠状动脉标本中，确定了粥样硬化侵蚀或破裂的部位。标本用针对肥大细胞的两种主要蛋白酶（类胰蛋白酶和糜酶）以及巨噬细胞、T淋巴细胞和平滑肌细胞的单克隆抗体进行染色。在侵蚀或破裂的直接部位，肥大细胞占所有有核细胞的6%，在相邻的粥样硬化区域占1%，在未受影响的内膜区域占0.1%。这些肥大细胞中被激活的比例，即已被刺激脱颗粒并释放其部分类胰蛋白酶和糜酶含量的比例，在侵蚀或破裂部位为86%，在相邻的粥样硬化区域为63%，在未受影响的内膜中为27%。在侵蚀或破裂部位，巨噬细胞和T淋巴细胞的数量也增加了，但平滑肌细胞的数量减少了。
在粥样硬化侵蚀或破裂部位，活化肥大细胞的聚集（比未受影响的冠状动脉内膜多200倍）表明，在血栓性冠状动脉闭塞中，肥大细胞发挥的作用是显著的。
