- Effect of Glucose Concentrations on the Cell Proliferation and Expression of L-type Calcium Channel mRNA in Cultured Rat Aortic Vascular Smooth Muscle Cells.
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Young Jung Cho, Hyung Joon Yoo, Hong Woo Nam, Ji Young Suh, In Kyung Jeong, Sung Hee Ihm, Hyeon Kyu Kim, Cheol Young Park, Jae Myung Yoo, Doo Man Kim, Moon Gi Choi, Sung Woo Park
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Korean Diabetes J. 2003;27(3):253-259. Published online June 1, 2003
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 Abstract
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- BACKGROUND
Vascular smooth muscle cell (VSMC) proliferation is one of the major pathogenic mechanisms for atherosclerosis. It is known that L-type calcium channels play a role in VSMC proliferation in diabetic rats. However, there have been no studies that show an association between the L-type calcium channels and the VSMC proliferation due to various glucose concentrations in the culture media. Therefore, the association between the voltage-dependent L-type calcium channels of the VSMCs, and the growth of vascular smooth muscle cells, was examined. METHODS: Rat aortic VSMCs were isolated from the aorta of Sprague-Dawley and OLETF rats, using an enzymic method. The VSMCs were cultured in various concentrations of glucose (5.5, 11.0, 16.6, 25, 30 and 40 mM). The VSMCs (1x10(4) cells in 24-well plates) were incubated in the presence of Bay K 8644 (10(-6)M), both with and without verapamil (10(-6)M), for 48 hours. The proliferation was then assessed by the MTT (methylthiazole tetrazolium) assay, and the expression of L-type calcium channel mRNA by RT-PCR. RESULTS: The vascular smooth muscle cell proliferation was significantly increased, in a dose-dependent manner, with glucose concentrations below 25 mM in both in a dose-dependent manner, with glucose concentrations below 25 mM in both kinds of rat. However, the increase in the VSMC proliferation of the OLETF rat was significantly higher than in the Sprague-Dawley rat. After the Bay K 8644 treatment, with the same glucose concentration, the VSMC proliferation and the expression of L-type calcium channel mRNA were significantly increased in both kinds of rat. After treatment with verapamil, the increased VSMC proliferation and expression of L-type calcium channel mRNA, due to the Bay K 8644, were suppressed to control levels in both kinds of rat. CONCLUSION: The results suggest that below certain concentrations of glucose, 25 mM, the L-type calcium channels may play a role in the VSMC proliferation of OLETF and Sprague-Dawley rats. The growth of the VSMCs in OLETF rats, due to various glucose concentrations (< 25 mM), was significantly higher than in the Sprague-Dawley rats.
- 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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