Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Center for Life Science Building, 3 Blackfan Circle, Boston, MA 02115, USA.
Microvasc Res. 2009 Dec;78(3):257-64. doi: 10.1016/j.mvr.2009.08.006. Epub 2009 Aug 27.
Survivin, an anti-apoptotic protein, can be induced by hypoxia and contributes to angiogenic activity in endothelial cells. To determine the potential mechanism of survivin in endothelial dysfunction caused by hyperglycemia in diabetes, we evaluated the role of survivin in hyperglycemia and its effect on endothelial homeostasis. We demonstrated that an increase of D-glucose was sufficient to down-regulate survivin expression, impacting survivin's angiogenic role in endothelial cells. We additionally showed that survivin expression was increased in response to hypoxia yet this reaction was mitigated when the endothelial cells were in hyperglycemic conditions prior to hypoxia. Hyperglycemia also affected survivin-related proliferation and migration of endothelial cells and increased the number of apoptotic cells. In the ischemic porcine myocardium, the expression of survivin was induced. Moreover, survivin expression in the aorta, myocardium, and isolated endothelial cells was attenuated in a porcine model of diabetes in comparison to non-diabetes, which correlated negatively with the levels of fasting blood sugars and positively with territory perfusion. These results demonstrate that hyperglycemia critically alters survivin expression in vitro and in vivo, which leads to attenuation of angiogenic activity and impacts endothelial metabolism.
Survivin 是一种抗凋亡蛋白，可被低氧诱导，并有助于内皮细胞的血管生成活性。为了确定 survivin 在糖尿病高血糖引起的内皮功能障碍中的潜在机制，我们评估了 survivin 在高血糖中的作用及其对血管内皮稳态的影响。我们证明，D-葡萄糖的增加足以下调 survivin 的表达，影响 survivin 在血管内皮细胞中的血管生成作用。我们还表明，缺氧会增加 survivin 的表达，但当内皮细胞在缺氧前处于高血糖状态时，这种反应会减轻。高血糖还会影响内皮细胞的增殖和迁移，并增加细胞凋亡的数量。在缺血性猪心肌中，survivin 的表达被诱导。此外，与非糖尿病相比，糖尿病猪模型中主动脉、心肌和分离的内皮细胞中的 survivin 表达减弱，这与空腹血糖水平呈负相关，与区域灌注呈正相关。这些结果表明，高血糖在体外和体内显著改变 survivin 的表达，导致血管生成活性减弱，并影响内皮代谢。
