Skip to main content
SpringerLink
Log in

Effects of Rosiglitazone on the Proliferation of Vascular Smooth Muscle Cell Induced by High Glucose

  • Published:
Cardiovascular Drugs and Therapy Aims and scope Submit manuscript

Abstract

Aim

To investigate the effects of the sensitizer rosiglitazone on the proliferation of vascular smooth muscle cell (VSMC) induced by high glucose administration.

Methods

VSMCs were isolated from rat thoracic aortas and cultured in 10% fetal bovine serum (FBS). VSMC proliferation was evaluated by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay and cell counting. The cell cycle was examined by flow cytometry. The protein expressions of proliferating cell nuclear antigen (PCNA) and matrix metalloproteinases-2 (MMP-2) were evaluated by Western blotting. MMP-2 mRNA expression was analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and gelatinolytic activity was determined by zymography.

Results

Promoted VSMC proliferation significantly increased the number of VSMCs in the S phase, the expressions of PCNA and MMP-2, and MMP-2 activity, as well as decreased the proportion of VSMCs in the G0/G1 phase. Rosiglitazone at a concentration of 10 μmol/L markedly inhibited glucose-induced VSMC proliferation (1.869 ± 0.22 vs 0.820 ± 0.15, P < 0.01). Concomitantly, rosiglitazone inhibited PCNA expression (0.96 ± 0.07 vs 0.75 ± 0.06, P < 0.05) and cell cycle progression from G0/G1 to S phase (the proportion of VSMCs in the G0/G1 and S phase were 69.6 ± 3.96% vs 84.3 ± 1.73% and 25.2 ± 1.73% vs 10.1 ± 1.42% (P < 0.01), respectively). Furthermore, rosiglitazone significantly decreased MMP-2 mRNA expression (0.98 ± 0.08 vs 0.71 ± 0.05, P < 0.05), protein expression (0.80 ± 0.04 vs 0.64 ± 0.03, P < 0.05) and MMP-2 activity (320 ± 25% vs 248 ± 21%, P < 0.05).

Conclusion

Rosiglitazone significantly inhibited VSMC proliferation, at least in part by inhibiting high glucose-induced G1→S phase transition, PCNA expression and MMP-2 synthesis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Massi-Benedetti M, Federici MO. Cardiovascular risk factors in type 2 diabetes: the role of hyperglycaemia. Exp Clin Endocrinol Diabetes 1999;107:S120–3.

    Article  PubMed  CAS  Google Scholar 

  2. Srivastava AK. High glucose-induced activation of protein kinase signaling pathways in vascular smooth muscle cells: a potential role in the pathogenesis of vascular dysfunction in diabetes. Int J Mol Med 2002;9:85–9.

    PubMed  CAS  Google Scholar 

  3. Rosenstock J, Sugimoto D, Strange P, Stewart J, Erika SR, Dailey G. Therapy in type 2 diabetes: insulin glargine or rosiglitazone added to combination therapy of sulfonylurea plus metformin in insulin-naïve patients. Diabetes Care 2006;29:554–9.

    Article  PubMed  CAS  Google Scholar 

  4. Regensteiner JG, Bauer TA, Reusch JE. Rosiglitazone improves exercise capacity in individuals with type 2 diabetes. Diabetes Care 2005;28:2877–83.

    Article  PubMed  CAS  Google Scholar 

  5. Kadoglou NP, Iliadis F, Angelopoulou N, Perrea D, Liapis CD, Alevizos M. Beneficial effects of Rosiglitazone on novel cardiovascular risk factors in patients with Type 2 diabetes mellitus. Diabet Med 2008;25:333–40.

    Article  PubMed  CAS  Google Scholar 

  6. Rohatgi A, McGuire DK. Effects of the thiazolidinedione medications on micro- and macrovascular complications in patients with diabetes—update 2008. Cardiovasc Drugs Ther. 2008;22, (in press).

  7. Tsuji T, Mizushige K, Noma T, Murakami K, Miyatake A, Kohno M. Improvement of aortic wall distensibility and reduction of oxidative stress by pioglitazone in pre-diabetic stage of Otsuka Long–Evans Tokushima fatty rats. Cardiovasc Drugs Ther 2002;16:429–34.

    Article  PubMed  CAS  Google Scholar 

  8. Wen JS, Hu B, Long G, Ling HY. Effects of rosiglitazone on blood glucose, blood lipid and vascular remodeling in rats fed with high fructose diet. Chin Pharmacol Bull 2004;20:571–5.

    CAS  Google Scholar 

  9. Iglarz M, Touyz RM, Amiri F, Lavoie MF, Diep QN, Schiffrin EL. Effect of peroxisome proliferator-activated receptor-a and -g activators on vascular remodeling in endothelin-dependent hypertension. Arterioscler Thromb Vasc Biol 2003;23:45–51.

    Article  PubMed  CAS  Google Scholar 

  10. Pistrosch F, Herbrig K, Oelschlaegel U, Richter S, Passauer J, Fischer S, et al. PPARgamma-agonist rosiglitazone increases number and migratory activity of cultured endothelial progenitor cells. Atherosclerosis 2005;183:163–7.

    Article  PubMed  CAS  Google Scholar 

  11. Ling HY, Feng SD, Zhou SH, Wang BX, Liu XQ, Hu B. Effects of rosiglitazone on aortic function in rats with insulin resistant-hypertension. Sheng Li Xue Bao 2005;57:125–31.

    PubMed  CAS  Google Scholar 

  12. Polikandriotis JA, Mazzella LJ, Rupnow HL, Michael HC. Peroxisome proliferator-activated receptor ligands stimulate endothelial nitric oxide production through distinct peroxisome proliferator-activated receptor-dependent mechanisms. Arterioscler Thromb Vasc Biol 2005;25:1810–6.

    Article  PubMed  CAS  Google Scholar 

  13. Hsieh PS, Hong LZ. Augmentation of nitric oxide is crucial for the time-dependent effects of rosiglitazone on blood pressure and baroreflex function in rats. J Hypertens 2008;26:83–92.

    PubMed  CAS  Google Scholar 

  14. Marx N, Froehlich J, Siam L, Ittner J, Wierse G, Schmidt A, et al. Antidiabetic PPAR gamma-activator rosiglitazone reduces MMP-9 serum levels in type 2 diabetic patients with coronary artery disease. Arterioscler Thromb Vasc Biol 2003;23:283–8.

    Article  PubMed  CAS  Google Scholar 

  15. Luo F, Wang ZH, Du LL, Wang J. Effects of PPAR-gamma agonist and MMP-2 on formation of atherosclerosis plaque in rabbits. Zhonghua Bing Li Xue Za Zhi 2007;36:556–7.

    PubMed  CAS  Google Scholar 

  16. Campbell JH, Kocher O, Skalli O, Gabbiani G, Campbell GR. Cytodifferentiation and expression of alpha-smooth muscle actin mRNA and protein during primary culture of aortic smooth muscle cells. Correlation with cell density and proliferative state. Arteriosclerosis 1989;9:633–43.

    PubMed  CAS  Google Scholar 

  17. Chiba K, Kawakami K, Tohyama K. Simultaneous evaluation of cell viability by neutral red, MTT and crystal violet staining assays of the same cells. Toxicol In Vitro 1998;12:251–8.

    Article  CAS  Google Scholar 

  18. Yang YB, Yang YX, Tang YL, Zhu BY, Hu ZW, Li YJ, et al. Probucol mediates vascular remodeling after percutaneous transluminal angioplasty via down-regulating ERK1/2 signal transduction pathway. Eur J Pharmacol 2007;570:125–34.

    Article  PubMed  CAS  Google Scholar 

  19. Su B, Yang YB, Tuo QH, Zhu BY, Win WD, Liao DF. Anti-apoptotic effects of probucol are associated with downregulation of Daxx expression in THP-1 macrophage. Cardiovasc Drugs Ther 2007;21:37–45.

    Article  PubMed  CAS  Google Scholar 

  20. Jimenez R, Hartwig W, Antoniu BA, Compton CC, Warshaw AL. Effect of matrix metalloproteinase inhibition on pancreatic cancer invasion and metastasis. Ann Surg 2000;231:644–54.

    Article  PubMed  CAS  Google Scholar 

  21. Wang QS, Guda K, Papanikolaou A, Dong M, Rosenberg DW. Expression of transforming growth factor beta1 and its type II receptor in mouse colon tumors induced by azoxymethane. Int J Oncol 2000;17:551–8.

    PubMed  CAS  Google Scholar 

  22. Haller H, Drab M, Luft FC. The role of hyperglycemia and hyperinsulinemia in the pathogenesis of diabetic angiopathy. Clin Nephrol 1996;46:246.

    PubMed  CAS  Google Scholar 

  23. Ginsberg H, Plutzky J, Sobel BE. A review of metabolic and cardiovascular effects of oral antidiabetic agents: beyond glucose level lowering. J Cardiovasc Risk 1999;6:337–46.

    PubMed  CAS  Google Scholar 

  24. Law RE, Goetz S, Xi XP, Jackson S, Kawano Y, Demer L, et al. Expression and function of PPAR-g in rat and human vascular smooth muscle cells. Circulation 2000;101:1311–8.

    PubMed  CAS  Google Scholar 

  25. Braun-Dullaeus RC, Mann MJ, Dzau VJ. Cell cycle progression: new therapeutic target for vascular proliferative disease. Circulation 1998;98:82–9.

    PubMed  CAS  Google Scholar 

  26. Yasui H, Sakurai H. Chemiluminescent detection and imaging of reactive oxygen species in live mouse skin exposed to UVA. Bioche Res Commun 2000;269:131–9.

    Article  CAS  Google Scholar 

  27. Laakso M. Hyperglycaemia and cardiovascular disease in type 2 diabetes mellitus. Diabetes 1999;48:937–42.

    Article  PubMed  CAS  Google Scholar 

  28. Pauly RR, Passaniti A, Bilato C, et al. Migration of cultured vascular smooth muscle cells through a basement membrane barrier requires type IV collagenase activity and is inhibited by cellular differentiation. Circ Res 1994;75:41–54.

    PubMed  CAS  Google Scholar 

  29. Mason DP, Kenagy RD, Hasenstab D, et al. Matrix metalloproteinase-9 overexpression enhances vascular smooth muscle cell migration and alters remodeling in the injured rat carotid artery. Circ Res 1999;85:1179–85.

    PubMed  CAS  Google Scholar 

  30. Clowes AW, Reidy MA, Clowes MM. Kinetics of cellular proliferation after arterial injury: smooth muscle growth in the absence of endothelium. Lab Invest 1983;49:327–33.

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors are indebted to Dr. Xuefeng Xia (University of Texas-Houston Health Science Center) for his valuable help in the preparation of the manuscript. This study was supported by grants from the Department of Education of Hunan Province (NO. 05C465), the National Natural Science Foundation of China (30770868), the National Major Basic Research Program (973 program) (2006CB503808) and the Natural Science Foundation of Hunan Province (NO. 01JJY2147).

Author information

Authors and Affiliations

  1. Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha, 410078, China

    Hong-Yan Ling & Duan-Fang Liao

  2. Department of Physiology, University of South China, Hengyang, 421001, China

    Hong-Yan Ling, Bi Hu & Shou-Hong Zhou

  3. Department of Physiology, Taishan Medical Collage, Taian, 271000, China

    Bing-Xiang Wang

  4. Division of Pharmacoproteomics, The Institute of Pharmacy & Pharmacology, University of South China, Hengyang, 421001, Hunan, People’s Republic of China

    Xu-Yu Zu, He-Sheng Ou & Duan-Fang Liao

  5. Department of Epidemiology, University of South China, Hengyang, 421001, China

    Shui-Dong Feng

Authors
  1. Hong-Yan Ling
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bi Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bing-Xiang Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xu-Yu Zu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shui-Dong Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. He-Sheng Ou
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shou-Hong Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Duan-Fang Liao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Duan-Fang Liao.

Additional information

Hong-Yan Ling and Bi Hu contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ling, HY., Hu, B., Wang, BX. et al. Effects of Rosiglitazone on the Proliferation of Vascular Smooth Muscle Cell Induced by High Glucose. Cardiovasc Drugs Ther 22, 453–460 (2008). https://doi.org/10.1007/s10557-008-6127-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10557-008-6127-6

Key words

Search

Navigation