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Alteration of mevalonate pathway in proliferated vascular smooth muscle from diabetic mice: possible role in high-glucose-induced atherogenic process.
- Source :
-
Journal of diabetes research [J Diabetes Res] 2015; Vol. 2015, pp. 379287. Date of Electronic Publication: 2015 Mar 30. - Publication Year :
- 2015
-
Abstract
- 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.
- Subjects :
- Acyl Coenzyme A metabolism
Alkyl and Aryl Transferases metabolism
Animals
Aorta metabolism
Blood Glucose metabolism
Cell Proliferation
Diabetes Mellitus, Experimental metabolism
Diabetes Mellitus, Experimental therapy
Farnesyltranstransferase metabolism
Female
Geranylgeranyl-Diphosphate Geranylgeranyltransferase metabolism
Geranyltranstransferase metabolism
Inflammation
Lipids chemistry
Mice
Mice, Inbred BALB C
Atherosclerosis metabolism
Glucose metabolism
Mevalonic Acid metabolism
Muscle, Smooth, Vascular metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2314-6753
- Volume :
- 2015
- Database :
- MEDLINE
- Journal :
- Journal of diabetes research
- Publication Type :
- Academic Journal
- Accession number :
- 25918730
- Full Text :
- https://doi.org/10.1155/2015/379287