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pubmed:abstractText |
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.
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pubmed:affiliation |
Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Center for Life Science Building, 3 Blackfan Circle, Boston, MA 02115, USA.
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