Overexpression of STAMP2 suppresses atherosclerosis and stabilizes plaques in diabetic mice.
Overexpression of STAMP2 suppresses atherosclerosis and stabilizes plaques in diabetic mice.
复制标题
STAMP2 过度表达可抑制糖尿病小鼠的动脉粥样硬化并稳定斑块
DOI：
10.1111/jcmm.12222
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发表时间：
2014-04
影响因子：
5.3
通讯作者：
Zhong M
中科院分区：
文献类型：
--
作者：
Wang J;Han L;Wang ZH;Ding WY;Shang YY;Tang MX;Li WB;Zhang Y;Zhang W;Zhong M
我们的研究旨在评估 STAMP2 基因（胰岛素抵抗（IR）的重要触发因素）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。通过一系列代谢和病理学测试来测量糖尿病小鼠的特征。通过RT-PCR和Western blot检测STAMP2的水平。通过组织病理学分析测量头臂动脉斑块面积、脂质和胶原含量，并通过TUNEL测量巨噬细胞凋亡。通过 Ad-STAMP2 转染和 STAMP2 siRNA 抑制验证了 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 的过度表达可改善 IR 并降低血糖水平。在头臂病变中，STAMP2的过表达显着降低了脂质含量、巨噬细胞数量和脆弱性指数。此外，病灶内的凋亡细胞和巨噬细胞数量均显着减少。在体外，高糖处理下 STAMP2 mRNA 和蛋白表达均增加。 STAMP2 过表达后，P-Akt 高表达，caspase-3 减少。然而，当 siRNA 抑制 STAMP2 时，p-Akt 蛋白的表达降低，caspase-3 表达增加。 STAMP2 过表达可以通过降低 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。
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.
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影响因子：
29
作者：
ten Freyhaus H;Calay ES;Yalcin A;Vallerie SN;Yang L;Calay ZZ;Saatcioglu F;Hotamisligil GS
通讯作者：
Hotamisligil GS
影响因子：
8
作者：
Korkmaz, CG;Korkmaz, KS;Saatcioglu, F
通讯作者：
Saatcioglu, F
影响因子：
37.8
作者：
Sun, Mei;Chen, Manyin;Liu, Peter P.
通讯作者：
Liu, Peter P.
影响因子：
6
作者：
Kolodgie, FD;Narula, J;Virmani, R
通讯作者：
Virmani, R
影响因子：
20.1
作者：
Verschuren L;Kooistra T;Bernhagen J;Voshol PJ;Ouwens DM;van Erk M;de Vries-van der Weij J;Leng L;van Bockel JH;van Dijk KW;Fingerle-Rowson G;Bucala R;Kleemann R
通讯作者：
Kleemann R