Silence of TRIB3 Suppresses Atherosclerosis and Stabilizes Plaques in Diabetic ApoE−/−/LDL Receptor−/− Mice
- Zhi-hao Wang1,
- Yuan-yuan Shang1,
- Shun Zhang2,
- Ming Zhong1,
- Xu-ping Wang1,
- Jing-ti Deng3,
- Jie Pan2,
- Yun Zhang1 and
- Wei Zhang1⇓
- 1Key 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, P.R. China
- 2Key Laboratory of Animal Resistance Biology of Shandong, College of Life Sciences, Shandong Normal University, Ji’nan, P.R. China
- 3Department of Anatomy, Medical School of Shandong University, Ji’nan, P.R. China
- Corresponding author: Wei Zhang, .
Z.-h.W. and Y.-y.S. contributed equally to this work.
Insulin resistance triggers the developments of diabetes mellitus and atherosclerosis. Tribbles homolog 3 (TRIB3) is involved in insulin resistance. We aimed to investigate whether TRIB3 is implicated in diabetic atherosclerosis. Sixty 3-week-old apolipoprotein E (ApoE−/−)/LDR receptor (LDLR−/−) mice were randomly divided into chow and diabetes groups. Diabetes was induced by a high-fat and high-sugar diet combined with low-dose streptozotocin. Mice in both groups were randomly divided into vehicle and TRIB3-silencing groups. After transfection, all mice were killed to evaluate the effects of TRIB3 on atherosclerosis. Silence of TRIB3 markedly decreased insulin resistance (P = 0.039) and glucose (P = 0.019), regardless of diabetes. Ultrasonography-measured parameters were similar in both groups, with and without silence of TRIB3. However, silence of TRIB3 decreased the aortic atherosclerotic burden (P = 1 × 10−13). Further study showed that in brachiocephalic lesions, fibrous cap thickness, cap-to-core ratio, collagen content, and the number of smooth muscle cells were significantly increased (P < 0.01 for all) by silence of TRIB3, whereas lipid and macrophage contents remained unaltered, with the vulnerability index significantly reduced. Moreover, the numbers of apoptotic cells and macrophages in brachiocephalic lesions were both significantly decreased (P < 0.01 for both). Macrophage migration was decreased (P = 4 × 10−4) by knocking down TRIB3, whereas adhesion and phagocytosis were increased (P < 0.05 for both). Silence of TRIB3 would diminish atherosclerotic burden and increase the plaque stability in diabetic mice.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db11-0518/-/DC1.
See accompanying commentary, p. 265.
- Received April 20, 2011.
- Accepted September 30, 2011.
- © 2012 by the American Diabetes Association.
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