Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Department of Cardiology, Qilu Hospital of Shandong University, Ji’nan, PR China.
Diabetes. 2012 Feb;61(2):463-73. doi: 10.2337/db11-0518.
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.
胰岛素抵抗会引发糖尿病和动脉粥样硬化的发生。TRIBS 同源物 3（TRIB3）参与胰岛素抵抗。我们旨在研究 TRIB3 是否与糖尿病性动脉粥样硬化有关。将 60 只 3 周龄的载脂蛋白 E（ApoE-/-）/低密度脂蛋白受体（LDLR-/-）小鼠随机分为普通饮食组和糖尿病组。糖尿病通过高脂肪和高糖饮食联合小剂量链脲佐菌素诱导。两组小鼠随机分为载体组和 TRIB3 沉默组。转染后，所有小鼠均被处死以评估 TRIB3 对动脉粥样硬化的影响。沉默 TRIB3 可显著降低胰岛素抵抗（P=0.039）和血糖（P=0.019），无论是否患有糖尿病。两组的超声测量参数相似，无论是否沉默 TRIB3。然而，沉默 TRIB3 可降低主动脉粥样硬化负担（P=1×10(-13)）。进一步研究表明，在肱动脉病变中，沉默 TRIB3 可显著增加纤维帽厚度、帽核比、胶原含量和平滑肌细胞数量（均 P<0.01），而脂质和巨噬细胞含量保持不变，易损性指数显著降低。此外，肱动脉病变中的凋亡细胞和巨噬细胞数量均显著减少（均 P<0.01）。沉默 TRIB3 可减少巨噬细胞迁移（P=4×10(-4)），而增加黏附和吞噬作用（均 P<0.05）。沉默 TRIB3 可减轻糖尿病小鼠的动脉粥样硬化负担并增加斑块稳定性。
