Human endothelial cells are defective in diabetic vascular disease.
Human endothelial cells are defective in diabetic vascular disease.
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人类内皮细胞在糖尿病血管疾病中存在缺陷。
DOI：
10.1006/jsre.1994.1195
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Tuan,TL
中科院分区：
文献类型：
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作者：
Sank,A;Wei,D;Reid,J;Ertl,D;Nimni,M;Weaver,F;Yellin,A;Tuan,TL
糖尿病血管病变的病理特征是内皮细胞（EC）增生和基底膜（BM）增厚。关于糖尿病血管疾病发病机制的一个关键问题是EC或BM或两者是否主要有缺陷并负责这些病理变化。以前的研究，采取了创造人工糖尿病条件的方法，一直没有定论。然而，已知细胞外基质可由于高血糖症而通过糖基化改变，从而改变EC功能。为了开始解决这个问题，并更密切地模拟体内情况，我们在细胞和分子水平上表征了从胰岛素依赖型糖尿病母亲（IDDM）中获得的人糖尿病EC。从正常和IDDM脐带中分离人EC，并使用粘附（%粘附细胞）、增殖（cpm/细胞）、剪切应力下抗分离性（保持粘附的细胞数）和葡萄糖摄取（cpm/2 × 104细胞）的标准测定评价细胞功能。通过北方分析定量主要BM组分（IV型胶原、层粘连蛋白β1和层粘连蛋白β2）的基因表达。糖尿病EC表现出增殖增加（与正常EC相比2 - 8倍），对剪切应力的抵抗力降低20-40%，并且比正常EC更慢地摄取葡萄糖10-15%。此外，北方分析显示，与正常细胞相比，糖尿病细胞中主要BM组分的表达平均增加10-18%。这些结果与体内观察结果和先前发表的数据一致。糖尿病EC在没有糖尿病或糖基化BM的情况下保留糖尿病特征表明，EC可能是DM中可能导致血管疾病发展的额外原发性缺陷的部位。
Diabetic vascular disease is characterized pathologically by endothelial cell (EC) hyperplasia and basement membrane (BM) thickening. One key question regarding the pathogenesis of diabetic vascular disease is whether the EC or BM or both are primarily defective and responsible for these pathological changes. Previous studies, which took the approach of creating artificial diabetic conditions, have been inconclusive. It is known, however, that the extracellular matrix may be altered by glycosylation as a result of hyperglycemia, thereby altering EC function. To begin to address this question and more closely mimic the situationin vivo, we characterized human diabetic EC harvested from insulin-dependent diabetic mothers (IDDM) at the cellular and molecular levels. Human EC were isolated from both normal and IDDM umbilical cords and cellular functions evaluated using standard assays of attachment (% attached cells), proliferation (cpm/cell), resistance to detachment under shear stress (number of cells remaining attached), and glucose uptake (cpm/2 × 104cells). Gene expression of major BM components (collagen type IV, laminin β1, and laminin β2) was quantified by Northern analysis. Diabetic EC demonstrated increased proliferation (two- to eightfold compared to normals), were 20-40% less resistant to shear stress and took up glucose 10-15% more slowly than normal EC. Furthermore, Northern analysis showed that the expression of major BM components was increased by an average of 10-18% in diabetic cells compared to normal cells. These results were consistent within vivoobservations and previously published data. The preservation of diabetic characteristics by diabetic EC in the absence of diabetic or glycosylated BM suggests that EC may be the site of an additional primary defect in DM that may contribute to the development of vascular diseases.