Overexpression of STAMP2 suppresses atherosclerosis and stabilizes plaques in diabetic mice

Authors

  • Jia Wang,

    1. 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
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  • Lu Han,

    1. 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
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  • Zhi-hao Wang,

    1. Department of Geriatric Medicine, Qilu Hospital of Shandong University, Ji'nan, China
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  • Wen-yuan Ding,

    1. 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
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  • Yuan-yuan Shang,

    1. 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
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  • Meng-xiong Tang,

    1. Department of Emergency Medicine, Qilu Hospital of Shandong University, Ji'nan, China
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  • Wen-bo Li,

    1. 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
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  • Yun Zhang,

    1. 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
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  • Wei Zhang,

    Corresponding author
    1. 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
    • Correspondence to: Wei Zhang, Ming Zhong,

      Department of Cardiology, Qilu Hospital of Shandong University, No.107 Wenhua West Road, Ji'nan 250012, China.

      Tel.: +86-531-82169339

      Fax: +86-531-86169356

      E-mails: zhongmingzm@gmail.com; weizhangsdu@sina.cn

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  • Ming Zhong

    Corresponding author
    1. 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
    • Correspondence to: Wei Zhang, Ming Zhong,

      Department of Cardiology, Qilu Hospital of Shandong University, No.107 Wenhua West Road, Ji'nan 250012, China.

      Tel.: +86-531-82169339

      Fax: +86-531-86169356

      E-mails: zhongmingzm@gmail.com; weizhangsdu@sina.cn

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Abstract

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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