Wang Jia, Han Lu, Wang Zhi-hao, Ding Wen-yuan, Shang Yuan-yuan, Tang Meng-xiong, Li Wen-bo, Zhang Yun, Zhang Wei, Zhong Ming
Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Chinese Ministry of Public Health, Department of Cardiology, Qilu Hospital of Shandong University, Ji'nan, China.
J Cell Mol Med. 2014 Apr;18(4):735-48. doi: 10.1111/jcmm.12222. Epub 2014 Jan 22.
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.
我们的研究旨在评估胰岛素抵抗（IR）的重要触发因素STAMP2基因的功能，并探讨其在糖尿病动脉粥样硬化易损斑块中巨噬细胞凋亡中的作用。通过一系列代谢物和病理学检测来测定糖尿病小鼠的特征。通过RT-PCR和蛋白质免疫印迹法测定STAMP2的水平。通过组织病理学分析测量头臂动脉斑块的斑块面积、脂质和胶原蛋白含量，并通过TUNEL法测定巨噬细胞凋亡。通过Ad-STAMP2转染和STAMP2 siRNA抑制验证STAMP2/Akt信号通路与巨噬细胞凋亡的相关性。糖尿病小鼠表现出IR、高血糖的典型特征。STAMP2的过表达改善了IR并降低了血糖水平。在头臂病变中，STAMP2的过表达显著降低了脂质含量、巨噬细胞数量和易损性指数。此外，病变中凋亡细胞和巨噬细胞的数量均显著减少。在体外，高糖处理下STAMP2的mRNA和蛋白质表达均增加。STAMP2过表达后，P-Akt高表达，caspase-3降低。然而，当STAMP2被siRNA抑制时，p-Akt蛋白表达降低，caspase-3增加。STAMP2过表达可通过降低IR和减少巨噬细胞凋亡对糖尿病动脉粥样硬化发挥保护作用。
