Long Term Effect of High Glucose and Phosphate Levels on the OPG/RANK/RANKL/TRAIL System in the Progression of Vascular Calcification in rat Aortic Smooth Muscle Cells.
10.4196/kjpp.2015.19.2.111
- Author:
Yang Ho KANG
1
;
Jung Sook JIN
;
Seok Man SON
Author Information
1. Division of Endocrinology and Metabolism, Department of Internal Medicine, Pusan National University School of Medicine, Yangsan 626-770, Korea. sonsm@pusan.ac.kr
- Publication Type:Original Article
- Keywords:
High glucose;
Osteoprotegerin;
Phosphate;
TNF-related apoptosis-inducing ligand;
Vascular calcification
- MeSH:
Alkaline Phosphatase;
Animals;
Atherosclerosis;
Axis, Cervical Vertebra;
Calcium;
Glucose*;
Muscle, Smooth, Vascular;
Myocytes, Smooth Muscle*;
NF-kappa B;
Osteoprotegerin;
Rats*;
Receptor Activator of Nuclear Factor-kappa B;
RNA, Messenger;
TNF-Related Apoptosis-Inducing Ligand;
Vascular Calcification*
- From:The Korean Journal of Physiology and Pharmacology
2015;19(2):111-118
- CountryRepublic of Korea
- Language:English
-
Abstract:
Osteoprotegerin (OPG), receptor activator of NF-kappaB ligand (RANKL)/receptor activator of NF-kappaB (RANK) axis, and TNF-related apoptosis-inducing ligand (TRAIL) participate in vascular calcification process including atherosclerosis, but their contributions under high glucose (HG) and phosphate (HP) condition for a long-term period (more than 2 weeks) have not been fully determined. In this study, we evaluated the effects of HG and HP levels over 2 or 4 weeks on the progression of vascular calcification in rat vascular smooth muscle cells (VSMCs). Calcium deposition in VSMCs was increased in medium containing HG (30 mmol/L D-glucose) with beta-glycerophosphate (beta-GP, 12 mmol/L) after 2 weeks and increased further after 4 weeks. OPG mRNA and protein expressions were unchanged in HG group with or without beta-GP after 2 weeks. However, after 4 weeks, OPG mRNA and protein expressions were significantly lower in HG group with beta-GP. No significant expression changes were observed in RANKL, RANK, or TRAIL during the experiment. After 4 weeks of treatment in HG group containing beta-GP and rhBMP-7, an inhibitor of vascular calcification, OPG expressions were maintained. Furthermore, mRNA expression of alkaline phosphatase (ALP), a marker of vascular mineralization, was lower in the presence of rhBMP-7. These results suggest that low OPG levels after long term HG and phosphate stimulation might reduce the binding of OPG to RANKL and TRAIL, and these changes could increase osteo-inductive VSMC differentiation, especially vascular mineralization reflected by increased ALP activity during vascular calcification.
