Selective Increase in Decorin Core mRNA Level in Cultured Vascular Smooth Muscle Cells after Exposure to Advanced Glycation Endproducts

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Although advanced glycation endproducts (AGEs) have been proved to be involved in the pathogenesis of vascular complications, such as atherosclerosis in diabetic patients, little is known about the functional damage to vascular cells caused by AGEs. In early and late atherosclerosis, excess proteoglycans (PGs) derived from vascular smooth muscle and endothelial cells deposit in the subendothelial extracellular matrix of the vascular wall. To address the question whether AGEs affect the synthesis of PGs in vascular cels or not, the effect of AGEs on steady-state levels of PG core mRNAs in cultured human aortic smooth muscle and endothelial cells was investigated. AGEs were prepared by incubation of bovine serum albumin with glucose and the mRNAs coding for the core proteins of heparan sulfate PGs (perlecan and syndecan-1) and chondroitin/dermatan sulfate PGs (versican, biglycan and decorin) were determined by quantitative reverse transcription-polymerase chain reactions. In vascular smooth muscle cells, the steady-state level of mRNAs coding for perlecan, syndecan-1,versican and biglycan core proteins was unchanged whereas that of mRNA coding for decorin core protein was increased by AGEs in a dose- and time-dependent manner. On the other hand, in vascular endothelial cells, mRNAs coding for perlecan, syndecan-1 and biglycan were observed, although their steady-state levels were unaffected by AGEs. The present data suggest that AGEs may be involved in the accumulation of decorin derived from vascular smooth muscle cells in the atherosclerotic vascular wall of diabetic patients.
社団法人日本薬学会の論文
2000-06-01

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