Alteration of Mevalonate Pathway in Proliferated Vascular Smooth Muscle from Diabetic Mice: Possible Role in High-Glucose-Induced Atherogenic Process
The proliferation of vascular smooth muscle cells (VSMCs) is one of the main features of atherosclerosis induced by high glucose. Mevalonate pathway is an important metabolic pathway that plays a key role in multiple cellular processes. The aim of this study was to define whether the enzyme expressi...
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Wiley
2015-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2015/379287 |
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| author | Guo-Ping Chen Xiao-Qin Zhang Tao Wu Liang Li Jie Han Chang-Qing Du |
| author_facet | Guo-Ping Chen Xiao-Qin Zhang Tao Wu Liang Li Jie Han Chang-Qing Du |
| author_sort | Guo-Ping Chen |
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| description | The proliferation of vascular smooth muscle cells (VSMCs) is one of the main features of atherosclerosis induced by high glucose. Mevalonate pathway is an important metabolic pathway that plays a key role in multiple cellular processes. The aim of this study was to define whether the enzyme expression in mevalonate pathway is changed in proliferated VSMCs during atherogenic process in diabetic mice. Diabetes was induced in BALB/c mice with streptozotocin (STZ, 50 mg/kg/day for 5 days). Induction of diabetes with STZ was associated with an increase of lesion area and media thickness after 8 and 16 weeks of diabetes. In aorta, there were overexpressions of some enzymes, including 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR), farnesyl pyrophosphate synthase (FPPS), geranylgeranyl pyrophosphate synthase (GGPPS), farnesyltransferase (FNT), and geranylgeranyltransferase-1 (GGT-1), and unchanged expression of squalene synthase (SQS) and phosphor-3-hydroxy-3-methylglutaryl-coenzyme A reductase (P-HMGR) in 8 and 16 weeks of diabetes. In vitro, VSMCs were cultured and treated with different glucose concentrations for 48 h. High glucose (22.2 mM) induced VSMC proliferation and upregulation of HMGR, FPPS, GGPPS, FNT, and GGT-1 but did not change the expressions of SQS and P-HMGR. In conclusion, altered expression of several key enzymes in the mevalonate pathway may play a potential pathophysiological role in atherogenic process of diabetes macrovascular complication. |
| format | Article |
| id | doaj-art-814bd1afd6874925a4dedf7bae49dcb7 |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-814bd1afd6874925a4dedf7bae49dcb72025-02-03T01:09:43ZengWileyJournal of Diabetes Research2314-67452314-67532015-01-01201510.1155/2015/379287379287Alteration of Mevalonate Pathway in Proliferated Vascular Smooth Muscle from Diabetic Mice: Possible Role in High-Glucose-Induced Atherogenic ProcessGuo-Ping Chen0Xiao-Qin Zhang1Tao Wu2Liang Li3Jie Han4Chang-Qing Du5Department of Endocrinology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, ChinaDepartment of Respirology, Zhejiang Provincial People’s Hospital, Hangzhou 310014, ChinaInstitute of Cardiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, ChinaInstitute of Cardiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, ChinaInstitute of Cardiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, ChinaDepartment of Cardiology, Zhejiang Hospital, Hangzhou 310003, ChinaThe proliferation of vascular smooth muscle cells (VSMCs) is one of the main features of atherosclerosis induced by high glucose. Mevalonate pathway is an important metabolic pathway that plays a key role in multiple cellular processes. The aim of this study was to define whether the enzyme expression in mevalonate pathway is changed in proliferated VSMCs during atherogenic process in diabetic mice. Diabetes was induced in BALB/c mice with streptozotocin (STZ, 50 mg/kg/day for 5 days). Induction of diabetes with STZ was associated with an increase of lesion area and media thickness after 8 and 16 weeks of diabetes. In aorta, there were overexpressions of some enzymes, including 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR), farnesyl pyrophosphate synthase (FPPS), geranylgeranyl pyrophosphate synthase (GGPPS), farnesyltransferase (FNT), and geranylgeranyltransferase-1 (GGT-1), and unchanged expression of squalene synthase (SQS) and phosphor-3-hydroxy-3-methylglutaryl-coenzyme A reductase (P-HMGR) in 8 and 16 weeks of diabetes. In vitro, VSMCs were cultured and treated with different glucose concentrations for 48 h. High glucose (22.2 mM) induced VSMC proliferation and upregulation of HMGR, FPPS, GGPPS, FNT, and GGT-1 but did not change the expressions of SQS and P-HMGR. In conclusion, altered expression of several key enzymes in the mevalonate pathway may play a potential pathophysiological role in atherogenic process of diabetes macrovascular complication.http://dx.doi.org/10.1155/2015/379287 |
| spellingShingle | Guo-Ping Chen Xiao-Qin Zhang Tao Wu Liang Li Jie Han Chang-Qing Du Alteration of Mevalonate Pathway in Proliferated Vascular Smooth Muscle from Diabetic Mice: Possible Role in High-Glucose-Induced Atherogenic Process Journal of Diabetes Research |
| title | Alteration of Mevalonate Pathway in Proliferated Vascular Smooth Muscle from Diabetic Mice: Possible Role in High-Glucose-Induced Atherogenic Process |
| title_full | Alteration of Mevalonate Pathway in Proliferated Vascular Smooth Muscle from Diabetic Mice: Possible Role in High-Glucose-Induced Atherogenic Process |
| title_fullStr | Alteration of Mevalonate Pathway in Proliferated Vascular Smooth Muscle from Diabetic Mice: Possible Role in High-Glucose-Induced Atherogenic Process |
| title_full_unstemmed | Alteration of Mevalonate Pathway in Proliferated Vascular Smooth Muscle from Diabetic Mice: Possible Role in High-Glucose-Induced Atherogenic Process |
| title_short | Alteration of Mevalonate Pathway in Proliferated Vascular Smooth Muscle from Diabetic Mice: Possible Role in High-Glucose-Induced Atherogenic Process |
| title_sort | alteration of mevalonate pathway in proliferated vascular smooth muscle from diabetic mice possible role in high glucose induced atherogenic process |
| url | http://dx.doi.org/10.1155/2015/379287 |
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