Preservation and structural adaptation of endothelium over experimental foam cell lesions. Quantitative ultrastructural study.
Preservation and structural adaptation of endothelium over experimental foam cell lesions. Quantitative ultrastructural study.
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实验性泡沫细胞损伤内皮的保存和结构适应。
DOI：
10.1161/01.atv.9.6.881
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发表时间：
1989
期刊：
影响因子：
--
通讯作者：
Zarins,CK
中科院分区：
文献类型：
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作者：
Taylor,KE;Glagov,S;Zarins,CK
为了评估高脂血症和内膜斑块形成对内皮细胞（EC）结构的改变程度，我们对食蟹猴在致动脉粥样硬化饮食3或6个月后的主动脉EC进行了定量超微结构研究。我们比较了无病变区（LFA）的EC与覆盖局灶离散泡沫细胞堆积（FDA）或覆盖多层融合斑块（MCP）的EC。与LFA相比，FDA或MCP的横截面管腔表面轮廓长度增加了15% (p < 0.005)，对应于直接下垫泡沫细胞的凸起轮廓。然而，单位表面积的EC数量没有增加（LFA为26.2 +/- 4.47 / 10(4)mm2， FDA为26.0 +/- 4.22），或者在横截面上，每100微米长度的内部弹性层（LFA为8.79 +/- 2.42，MCP为8.26 +/- 2.01）。通过LFA或MCP，每个细胞接触周围细胞的数量也与正常血脂对照组（LFA组为6.56 +/- 0.85，MCP组为5.58 +/- 0.86）没有差异。大多数EC在病变上明显减弱，虽然相邻EC之间横向接触区域的范围和复杂性降低，但基底动脉投射的数量和复杂性大大增加。这些结构在内膜泡沫细胞之间延伸，插入到内部弹性层或内膜基质纤维上，导致EC轮廓的腹腔部分长度增加2.7倍。因此，横向EC轮廓的周长从LFA的41.4 +/- 2.12微米增加到MCP的82.2 +/- 5.21微米（p小于0.0001）。随着病变的发展，EC在血流方向的极化减弱。长宽比以及该比值的标准差从LFA的3.51 +/- 3.92下降到MCP的2.35 +/- 0.25，这主要是由于细胞周长暴露于管腔的比例增加。在正常血脂对照组或紧挨着斑块的LFA中，病变定位与EC在相应位置的取向无关。高脂血症动物的EC细胞器在所有区域显示出代谢活性增加的特征，并且在病变减弱的EC中应力丝增加。无论病变位置、大小或复杂程度如何，均无EC变性、坏死或脱落的证据。
To assess the extent to which endothelial cell (EC) structure is modified by hyperlipidemia and by the formation of intimal plaques, we undertook a quantitative ultrastructural study of aortic EC of cynomolgus monkeys after 3 or 6 months on an atherogenic diet. We compared EC in lesion-free areas (LFA) with EC overlying focal discrete foam cell accumulations (FDA) or covering multilayered confluent plaques (MCP). There was a 15% increase in cross-sectional lumen surface profile length over FDA or MCP compared to LFA (p less than 0.005) corresponding to the bulging contours of immediately underlying foam cells. There was, however, no increase in the number of EC per unit of surface area (26.2 +/- 4.47 per 10(4) mm2 for LFA and 26.0 +/- 4.22 for FDA) or, on cross-section, per 100 microns length of underlying internal elastic lamina (8.79 +/- 2.42 for LFA, 8.26 +/- 2.01 for MCP). Nor did the number of surrounding cells contacted by each cell over LFA or MCP differ from normolipemic controls (6.56 +/- 0.85 for LFA and 5.58 +/- 0.86 for MCP). Most ECs were markedly attenuated over lesions, and while the extent and complexity of lateral contact regions between adjacent EC was diminished, the number and complexity of basilar projections was greatly increased. These structures extended among the intimal foam cells to insert on the internal elastic lamina or on intimal matrix fibers, resulting in a 2.7-fold increase in the length of the abluminal portion of the EC profile. The perimeter of the transverse EC profiles was thereby increased from 41.4 +/- 2.12 microns in LFA to 82.2 +/- 5.21 microns over MCP (p less than 0.0001). Polarization of EC in the direction of flow diminished as lesions developed. The ratio of length to width, as well as the standard deviation of the ratio, decreased from 3.51 +/- 3.92 in LFA to 2.35 +/- 0.25 over MCP, due mainly to increases in the proportion of the cell perimeter exposed to the lumen. Lesion localization bore no relationship to the orientation of EC in corresponding locations in the normolipemic controls or in LFA immediately adjacent to plaques. Organelles of EC in hyperlipidemic animals showed features suggestive of increased metabolic activity in all regions, and stress filaments were increased in the EC attenuated over lesions. There was no evidence of EC degeneration, necrosis, or sloughing regardless of lesion location, size, or complexity.