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Cell Biological Study on Abnormal Proteoglycan Synthesis in Vascular Cells Exposed to Heavy Metals

机译:重金属暴露于血管细胞蛋白聚糖异常合成的细胞生物学研究

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摘要

Lead and cadmium are toxic heavy metals that have been shown to be possible risk factors of atherosclerosis in epidemiological and experimental studies. Since excess extracellular matrix, including proteoglycans, accumulates changing the composition and the structure in the atherosclerotic vascular wall, the effects of lead and cadmium on the proteoglycan synthesis in vascular cells have been studied using a cell culture system. The following results were obtained: Lead does not destroy endothelial cell layers but markedly inhibits the repair of the injured cell layers, which results from a lower response to endogenous basic fibroblast growth factor caused by inhibition of the synthesis of perlecan, a large heparan sulfate proteoglycan, in vascular endothelial cells. Lead selectively inhibits the synthesis of versican, a large chondroitin sulfate proteoglycan, in vascular smooth muscle cells only at a high cell density. Cadmium induces the synthesis of biglycan and decorin, small dermatan sulfate proteoglycans, in vascular smooth muscle cells only at a low cell density, while inhibiting the synthesis of other proteoglycan molecules. It is therefore suggested that lead and cadmium may influence the developmental process of atherosclerosis through disrupting the regulation of proteoglycan synthesis in vascular cells.
机译:铅和镉是有毒的重金属,在流行病学和实验研究中已被证明可能是动脉粥样硬化的危险因素。由于包括蛋白聚糖在内的过多的细胞外基质会累积改变动脉粥样硬化血管壁的组成和结构,因此已使用细胞培养系统研究了铅和镉对血管细胞蛋白聚糖合成的影响。获得了以下结果:铅不会破坏内皮细胞层,但会显着抑制受损细胞层的修复,这是由于对珍珠岩(一种大型硫酸乙酰肝素蛋白聚糖)的合成的抑制导致对内源性碱性成纤维细胞生长因子的响应降低所致。 ,在血管内皮细胞中。铅仅以高细胞密度选择性抑制血管平滑肌细胞中versican(一种大的硫酸软骨素蛋白聚糖)的合成。镉仅在低细胞密度下诱导血管平滑肌细胞中双糖链蛋白聚糖和小蛋白聚糖,硫酸皮肤素小蛋白聚糖的合成,同时抑制其他蛋白聚糖分子的合成。因此,建议铅和镉可能通过破坏血管细胞中蛋白聚糖合成的调控来影响动脉粥样硬化的发展过程。

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