- Effect of Advanced Glycation End Products on Rat Aortic Vascular Smooth Muscle Cells.
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Jin Young Song, Sung Hee Ihm, Ji Young Suh, Young Joong Cho, Hyung Joon Yoo, Sung Woo Park, Ja Hei Ihm
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Korean Diabetes J. 2002;26(2):91-99. Published online April 1, 2002
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 Abstract
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- BACKGROUND
Diabetes mellitus is an epidemiologically proven risk factor for atherosclerosis. Advanced glycation end products (AGE) have been implicated in the pathogenesis of many diabetic vascular complications. AGE not only change the physicochemical properties of proteins, but also induce a wide range of cell-mediated responses. However, biological effects of AGE on the vascular smooth muscle cells (VSMCs) have not been fully explained despite of presence of an AGE-receptor on the VSMCs. METHODS: In order to test whether AGE promotes atherosclerosis by stimulation of the growth promoting signal transduction pathways in the VSMCs, the proliferation of rat aortic VSMCs cultured in the presence of AGE-BSA with/without anti-AGE antibodies, the MAP kinase inhibitor and antioxidants was measured. The VSMCs (1 x 104 cells in 24-well plates) isolated from the aorta of Sprague-Dawley rats were incubated for 48 hours and the proliferation was assessed by a MTT assay. RESULTS: AGE-BSA increased the proliferation of rat aortic VSMCs by 1.5~1.6 fold at the g/mL level. The stimulatory effect of AGE-BSA (5 microgram/mL) was blocked by the anti-AGE antibodies (100 microgram/mL). PD98059 at 50 M inhibited the AGE - BSA - induced VSMC proliferation, suggesting that MAP kinase activation might be responsible for the proliferative response of the VSMCs to AGE. AGE - BSA - induced VSMC proliferation was also attenuated by N-acetylcysteine (1 micro M) and butylated hydroxyanisole (10 micro M), implying that increased intracellular oxidative stress might be also involved in the proliferative response to AGE. CONCLUSION: These results suggest AGE play a role in diabetic atherosclerosis by stimulating of the growth promoting signal transduction pathways in the VSMCs.
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KDA
