Bauriedel G, Kandolf R, Schluckebier S, Welsch U
Department of Internal Medicine, Klinikum Grosshadern, Institute of Anatomy, University of Munich, Germany.
Am J Cardiol. 1996 Mar 1;77(7):468-74. doi: 10.1016/s0002-9149(97)89339-3.
In animal studies, smooth muscle cell phenotype conversion has been suggested to be an essential prerequisite for subsequent migratory and proliferative events leading to (neo)intima formation. To determine ultrastructural characteristics of individual smooth muscle cells and to relate them to specific lesion types and intimal cell density, we compared atherectomy samples from 17 restenotic and 32 primary coronary and peripheral lesions using transmission electron microscopy and histology. Ultrastructural analysis of cell-rich tissue, predominantly of restenotic origin, revealed smooth muscle cells full of synthetic organelles. Moreover, these cells were frequently found to be surrounded by loose extracellular matrix and partially fragmented basement membrane components. In contrast, plaques exhibiting low cell density, as exclusively seen with primary lesions, displayed an extensive buildup of extracellular matrix containing sparse numbers of microfilament-rich smooth muscle cells. The central finding of our study is a morphometrically quantitated, twofold greater (p <0.001) volume fraction of synthetic organelles (VS) within smooth muscle cells in restenotic versus primary plaques, indicating a more dedifferentiated cellular phenotype as a typical feature of restenotic lesions. Equally enhanced VS values were seen for restenotic coronary and peripheral plaques. No VS decrease was observed during time after angioplasty (2.2 to 30 months) regardless of previous revascularization procedures (balloon angioplasty or atherectomy). Despite intra- and interlesional variability, VS and intimal cell density were strongly correlated (r = 0.74; p <0.001). This correlation was observed more often with clinical restenoses and, importantly, in a portion (10% to 15%) of primary lesions. Data from restenotic lesions indicate that a dedifferentiated smooth muscle cell phenotype, pericellular matrix disintegration, and intimal hypercellularity are long-lasting biologic responses to previous smooth muscle cell injury. Similar tissue characteristics expressed in several primary lesions suggest that comparable pathogenic mechanisms are related to the progression and/or acuity of chronic lesions.
在动物研究中，平滑肌细胞表型转化被认为是导致（新）内膜形成的后续迁移和增殖事件的必要前提条件。为了确定单个平滑肌细胞的超微结构特征，并将其与特定病变类型和内膜细胞密度相关联，我们使用透射电子显微镜和组织学方法比较了17例再狭窄以及32例原发性冠状动脉和周围血管病变的旋切术样本。对富含细胞的组织（主要来自再狭窄病变）进行的超微结构分析显示，平滑肌细胞充满了合成细胞器。此外，这些细胞经常被疏松的细胞外基质和部分破碎的基底膜成分所包围。相比之下，仅在原发性病变中出现的细胞密度低的斑块，显示出含有少量富含微丝的平滑肌细胞的细胞外基质大量堆积。我们研究的主要发现是，通过形态计量学定量分析，再狭窄斑块中的平滑肌细胞内合成细胞器的体积分数（VS）比原发性斑块中的高出两倍（p<0.001），这表明去分化程度更高的细胞表型是再狭窄病变的典型特征。再狭窄的冠状动脉和周围血管斑块的VS值同样升高。无论先前的血运重建程序（球囊血管成形术或旋切术）如何，在血管成形术后的一段时间内（2.2至30个月）均未观察到VS降低。尽管病变内和病变间存在变异性，但VS与内膜细胞密度仍密切相关（r = 0.74；p<0.001）。这种相关性在临床再狭窄中更常见，重要的是，在一部分（10%至15%）的原发性病变中也观察到了。来自再狭窄病变的数据表明，去分化的平滑肌细胞表型、细胞周围基质解体和内膜细胞增多是对先前平滑肌细胞损伤的长期生物学反应。在一些原发性病变中表现出的类似组织特征表明，类似的致病机制与慢性病变的进展和/或严重程度有关。
