Abstract
Aim:
To evaluate the effects of angiopoietin-1 (Ang-1) on myocardial endothelial cell function under high glucose (HG) condition.
Methods:
Mouse heart myocardial endothelial cells (MHMECs) were cultured and incubated under HG (25 mmol/L) or normal glucose (NG, 5 mmol/L) conditions for 72 h. MTT was used to determine cellular viability, and TUNEL assay and caspase-3 enzyme linked immunosorbent assays were used to assay endothelial apoptosis induced by serum starvation. Immunoprecipitation and Western blot analysis were used to analyze protein phosphorylation and expression. Endothelial tube formation was used as an in vitro assay for angiogenesis.
Results:
Exposure of MHMECs to HG resulted in dramatic decreases in phosphorylation of the Tie-2 receptor and its downstream signaling partners, Akt/eNOS, compared to that under NG conditions. Ang-1 (250 ng/mL) increased Tie-2 activation, inhibited cell apoptosis, and promoted angiogenesis. Ang-1-mediated protection of endothelial function was blunted by Ang-2 (25 ng/mL).
Conclusion:
Ang-1 activates the Tie-2 pathway and restores hyperglycemia-induced myocardial microvascular endothelial dysfunction. This suggests a protective role of Ang-1 in the ischemic myocardium, particularly in hearts affected by hyperglycemia or diabetes.
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Acknowledgements
This work was supported by grants from the American Heart Association (0565196B) and the NIH (DK074995 and R01HL102042), the National Natural Science Foundation of China (No 30971170, 30770868, 30971267, and 30600249), and the Outstanding Youth Foundation of Education Department in Hunan Province (09B089).
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Tuo, Qh., Xiong, Gz., Zeng, H. et al. Angiopoietin-1 protects myocardial endothelial cell function blunted by angiopoietin-2 and high glucose condition. Acta Pharmacol Sin 32, 45–51 (2011). https://doi.org/10.1038/aps.2010.183
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DOI: https://doi.org/10.1038/aps.2010.183
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