Rosenfeld M E, Carew T E, von Hodenberg E, Pittman R C, Ross R, Steinberg D
Division of Endocrinology and Metabolism, University of California, San Diego, La Jolla 92093.
Arterioscler Thromb. 1992 Aug;12(8):985-95. doi: 10.1161/01.atv.12.8.985.
It is well established that plasma lipoproteins enter the artery wall and play a role in the atherogenic process. However, it is still unclear where within developing atherosclerotic lesions lipoproteins accumulate and which arterial cells participate in the metabolism of these lipoproteins. For this reason, light and electron microscopic autoradiograms were prepared from sections of lesioned aortas of Watanabe heritable hyperlipidemic (WHHL) rabbits 44 hours after injection of 125I-tyramine cellobiose-low density lipoprotein (TC-LDL). After uptake of 125I-TC-LDL and intracellular degradation of the LDL protein, the nondegradable TC ligand remains trapped and thus demarcates the cells participating in the degradation of LDL. Results of other studies indicate that 48 hours after injection into WHHL rabbits, about one half of the 125I label present in lesions represents accumulated degradation products while the remaining 125I label is present as intact 125I-TC-LDL. The distribution of autoradiographic silver grains was analyzed at low resolution in fatty streaks, transitional lesions, and advanced atheroma. In all cases, the majority of silver grains were associated with superficially located subendothelial macrophage-derived foam cells. In more advanced lesions, labeling was predominant in foam cells situated within the lateral margins of the lesions. Morphometric quantification of the distribution of silver grains in electron photomicrographs of fatty streaks from two young WHHL rabbits strongly supported the data obtained at the light microscopic level. In early fatty streaks from the aortic arch and the thoracic and abdominal aortas, subendothelial macrophage-derived foam cells contained a high proportion of the silver grains (40-60% of the total) and accounted for between 30% and 40% of the lesion volume. In contrast, smooth muscle cells in the lesions contained only 7-10% of the total silver grains and accounted for approximately 20% of the lesion volume. Endothelial cells contained the most silver grains on a per-unit-volume basis by occupying only 1-2% of the lesion volume. However, the endothelium contained less than 5% of the total grains in lesions. The remaining silver grains (25-45%) were associated with the extracellular matrix, which constituted between 40% and 50% of the lesion volume. These data indicate that in the WHHL rabbit, subendothelial macrophage-derived foam cells avidly accumulate and metabolize LDL despite having few functional LDL receptors.
血浆脂蛋白进入动脉壁并在动脉粥样硬化形成过程中发挥作用，这一点已得到充分证实。然而，脂蛋白在动脉粥样硬化病变发展过程中具体在何处积聚，以及哪些动脉细胞参与这些脂蛋白的代谢，目前仍不清楚。因此，在给渡边遗传性高脂血症（WHHL）兔注射125I-酪胺纤维二糖-低密度脂蛋白（TC-LDL）44小时后，从病变主动脉切片制备了光镜和电镜放射自显影片。在摄取125I-TC-LDL并使LDL蛋白在细胞内降解后，不可降解的TC配体仍被困住，从而界定了参与LDL降解的细胞。其他研究结果表明，在给WHHL兔注射后48小时，病变中存在的125I标记物约一半代表积累的降解产物，而其余的125I标记物以完整的125I-TC-LDL形式存在。在低分辨率下分析了脂肪条纹、过渡性病变和晚期动脉粥样硬化中放射自显影片银颗粒的分布。在所有情况下，大多数银颗粒都与位于表面的内皮下巨噬细胞衍生的泡沫细胞相关。在更晚期的病变中，标记主要出现在病变边缘的泡沫细胞中。对两只年轻WHHL兔脂肪条纹的电子显微照片中银颗粒分布进行形态计量学定量分析，有力地支持了在光镜水平获得的数据。在主动脉弓以及胸主动脉和腹主动脉的早期脂肪条纹中，内皮下巨噬细胞衍生的泡沫细胞含有高比例的银颗粒（占总数的40 - 60%），占病变体积的30%至40%。相比之下，病变中的平滑肌细胞仅含有总数7 - 10%的银颗粒，并占病变体积的约20%。内皮细胞按单位体积计算含有最多的银颗粒，但仅占病变体积的1 - 2%。然而，内皮细胞在病变中所含的颗粒不到总数的5%。其余的银颗粒（25 - 45%）与细胞外基质相关，细胞外基质占病变体积的40%至50%。这些数据表明，在WHHL兔中，内皮下巨噬细胞衍生的泡沫细胞尽管功能性LDL受体很少，但仍能大量积聚并代谢LDL。
