Overexpression of STAMP2 suppresses atherosclerosis and stabilizes plaques in diabetic mice
Article first published online: 22 JAN 2014
© 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Journal of Cellular and Molecular Medicine
Volume 18, Issue 4, pages 735–748, April 2014
How to Cite
Wang, J., Han, L., Wang, Z.-h., Ding, W.-y., Shang, Y.-y., Tang, M.-x., Li, W.-b., Zhang, Y., Zhang, W. and Zhong, M. (2014), Overexpression of STAMP2 suppresses atherosclerosis and stabilizes plaques in diabetic mice. Journal of Cellular and Molecular Medicine, 18: 735–748. doi: 10.1111/jcmm.12222
- Issue published online: 8 APR 2014
- Article first published online: 22 JAN 2014
- Manuscript Accepted: 29 NOV 2013
- Manuscript Received: 15 SEP 2013
- Independent Innovation Foundation of Shandong University. Grant Number: 2012JC034
- Natural Science Foundation of Shandong Province. Grant Numbers: ZR2009CM022, ZR2009CM025
- National Natural Science Foundation of China. Grant Numbers: 30971215, 81070141, 81070192, 81100605, 81270352, 81270287
- National Basic Research Program of China. Grant Number: 2013CB530700
- Key Technologies R & D Program of Shandong Province. Grant Number: 2010G0020262
- STAMP2/Akt signalling pathway;
- apoptosis of macrophage;
- Type 2 diabetes mellitus;
- insulin resistance;
- vulnerable plaque;
Our research aims to evaluate the function of the STAMP2 gene, an important trigger in insulin resistance (IR), and explore its role in macrophage apoptosis in diabetic atherosclerotic vulnerable plaques. The characteristics of diabetic mice were measured by serial metabolite and pathology tests. The level of STAMP2 was measured by RT-PCR and Western blot. The plaque area, lipid and collagen content of brachiocephalic artery plaques were measured by histopathological analyses, and the macrophage apoptosis was measured by TUNEL. Correlation of STAMP2/Akt signaling pathway and macrophage apoptosis was validated by Ad-STAMP2 transfection and STAMP2 siRNA inhibition. The diabetic mice showed typical features of IR, hyperglycaemia. Overexpression of STAMP2 ameliorated IR and decreased serum glucose level. In brachiocephalic lesions, lipid content, macrophage quantity and the vulnerability index were significantly decreased by overexpression of STAMP2. Moreover, the numbers of apoptotic cells and macrophages in lesions were both significantly decreased. In vitro, both mRNA and protein expressions of STAMP2 were increased under high glucose treatment. P-Akt was highly expressed and caspase-3 was decreased after overexpression of STAMP2. However, expression of p-Akt protein was decreased and caspase-3 was increased when STAMP2 was inhibited by siRNA. STAMP2 overexpression could exert a protective effect on diabetic atherosclerosis by reducing IR and diminishing macrophage apoptosis.