Angiopoietin-1 protects myocardial endothelial cell function blunted by angiopoietin-2 and high glucose condition.
OBJECTIVE
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).


CONCLUSIONS
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.
Department of Pediatrics, Division of Neonatology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Qin-hui
QH
Tuo
Guo-zuo
GZ
Xiong
Heng
H
Zeng
Hei-di
HD
Yu
Shao-wei
SW
Sun
Hong-yan
HY
Ling
Bing-yang
BY
Zhu
Duan-fang
DF
Liao
Jian-xiong
JX
Chen
D042683:Angiopoietin-1 / Q000378:metabolism*; D042702:Angiopoietin-2 / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D051379:Mice; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D042787:Receptor, TIE-2 / Q000378:metabolism
D042683:Angiopoietin-1; D042702:Angiopoietin-2; D042787:Receptor, TIE-2; D005947:Glucose