Holland J A, Pritchard K A, Rogers N J, Stemerman M B
Department of Medicine, New York Medical College, Valhalla.
Am J Pathol. 1992 Mar;140(3):551-8.
Cultured human umbilical vein endothelial cells (EC) exposed to atherogenic low-density lipoprotein (LDL) levels for protracted periods demonstrated heightened endocytosis. Confluent EC were incubated with LDL 90 to 240 mg/dl cholesterol for 1 to 4 days and endocytosis was measured by 14C-sucrose uptake. Control EC and cells incubated with 90 mg/dl LDL cholesterol showed similar uptakes of 14C-sucrose during all measured time periods. In contrast, EC exposed to 240 mg/dl LDL cholesterol showed an increase in endocytosis beginning at 2 days, whereas 160 mg/dl LDL cholesterol promoted increased uptake by 4 days. The endocytotic activity of LDL-perturbed EC is reduced to levels seen in control cells by cytochalasin B, an actin polymerization inhibitor. This finding suggests a modulatory role for the cytoskeleton in endocytosis changes. Examination of LDL-perturbed EC cytoskeleton reveals structural remodeling resulting in a marked increase in stress fibers. Cytochalasin B exposure causes a loss of stress fibers with the formation of globular filamental aggregates. Such LDL-induced cellular functional changes may contribute mechanistically to endothelial dysfunction, which is widely held to be a major contributing factor in the pathogenesis of atherosclerosis.
长期暴露于致动脉粥样硬化低密度脂蛋白（LDL）水平的培养人脐静脉内皮细胞（EC）表现出内吞作用增强。将融合的内皮细胞与含90至240mg/dl胆固醇的LDL孵育1至4天，通过14C-蔗糖摄取来测量内吞作用。对照内皮细胞以及与90mg/dl LDL胆固醇孵育的细胞在所有测量时间段内14C-蔗糖摄取量相似。相比之下，暴露于240mg/dl LDL胆固醇的内皮细胞在第2天开始内吞作用增加，而160mg/dl LDL胆固醇在第4天促进摄取增加。肌动蛋白聚合抑制剂细胞松弛素B可将受LDL干扰的内皮细胞的内吞活性降低至对照细胞中的水平。这一发现表明细胞骨架在内吞作用变化中具有调节作用。对受LDL干扰的内皮细胞骨架的检查显示结构重塑，导致应力纤维显著增加。暴露于细胞松弛素B会导致应力纤维消失并形成球状丝状聚集体。这种由LDL诱导的细胞功能变化可能在机制上导致内皮功能障碍，而内皮功能障碍被广泛认为是动脉粥样硬化发病机制中的一个主要促成因素。
