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Abstract：
Atherosclerosis remains a major cause of mortality. Whereas the histopathological progression of atherosclerotic lesions is well documented, much less is known about the development of unstable or vulnerable plaque, which can rupture leading to thrombus, luminal occlusion and infarct. Apoptosis in the fibrous cap, which is rich in vascular smooth muscle cells (VSMCs) and macrophages, and its subsequent weakening or erosion seems to be an important regulator of plaque stability. The aim of our study was to improve our knowledge on the biological mechanisms that cause plaque instability in order to develop new therapies to maintain atherosclerotic plaque stability and avoid its rupture. In our study, we collected surgical specimens from atherosclerotic plaques in the right or left internal carotid artery of 62 patients with evident clinical symptoms. Histopathology and histochemistry were performed on wax-embedded sections. Immunohistochemical localization of caspase-3, N-cadherin and ADAM-10 was undertaken in order to highlight links between apoptosis, as expressed by caspase-3 immunostaining, and possible roles of N-cadherin, a cell-cell junction protein in VSMCs and macrophages that provides a pro-survival signal reducing apoptosis, and ADAM-10, a \"disintegrin and metalloproteases\" that is able to cleave N-cadherin in glioblastomas. Our results showed that when apoptosis, expressed by caspase-3 immunostaining, increased in the fibrous cap, rich in VSMCs and macrophages, the expression of N-cadherin decreased. The decreased N-cadherin expression, in turn, was linked to increased ADAM-10 expression. This study shows that apoptotic events are probably involved in the vulnerability of atherosclerotic plaque.
摘要：
动脉粥样硬化仍然是死亡的主要原因。而动脉粥样硬化病变的组织病理学进展是有据可查的，对不稳定或易损斑块的发展知之甚少，会破裂导致血栓，管腔闭塞和梗死。纤维帽细胞凋亡，富含血管平滑肌细胞（VSMC）和巨噬细胞，其随后的弱化或侵蚀似乎是斑块稳定性的重要调节剂。我们研究的目的是提高我们对导致斑块不稳定的生物学机制的认识，以开发新的疗法来维持动脉粥样硬化斑块的稳定性并避免其破裂。在我们的研究中,我们收集了62例有明显临床症状的患者的右或左颈内动脉粥样硬化斑块的手术标本。在蜡包埋切片上进行组织病理学和组织化学。进行caspase-3，N-cadherin和ADAM-10的免疫组织化学定位，以突出凋亡之间的联系。通过caspase-3免疫染色表达，以及N-钙粘蛋白的可能作用，VSMC和巨噬细胞中的一种细胞-细胞连接蛋白，可提供减少凋亡的促存活信号，和ADAM-10，一种“解整合素和金属蛋白酶”，能够在胶质母细胞瘤中切割N-钙黏着蛋白。我们的结果表明，当细胞凋亡时，通过caspase-3免疫染色表达，在纤维帽增加，富含VSMC和巨噬细胞，N-cadherin的表达降低。N-cadherin表达降低，反过来,与ADAM-10表达增加有关。这项研究表明，凋亡事件可能与动脉粥样硬化斑块的易损性有关。
