کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1994720 1541280 2016 25 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
FoxO3α-mediated autophagy contributes to apoptosis in cardiac microvascular endothelial cells under hypoxia
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
FoxO3α-mediated autophagy contributes to apoptosis in cardiac microvascular endothelial cells under hypoxia
چکیده انگلیسی
Hypoxic injury of cardiac microvascular endothelial cells (CMECs) is an important pathophysiological event in myocardial infarction, whereas, the underlying mechanism is still poorly understood. Autophagy, a highly conserved process of cellular degradation, is required for normal cardiac function and also has been implicated in various cardiovascular diseases. Here we investigated the potential role of autophagy in CMEC dysfunction under hypoxia. CMECs were isolated from SD rats. Hypoxia (6-24 h, 1% O2) induced autophagy in CMECs as evidenced by formation of punctate LC3, increased conversion of LC3-I to LC3-II and increased p62 degradation. Importantly, hypoxia-induced apoptosis in CMECs was attenuated by 3-Methyladenine (5 mM), an autophagy inhibitor, and aggravated by rapamycin (1.0 μg/L), an autophagy inducer. Meanwhile, hypoxia increased the nuclear localization of FoxO3α, accompanying with the decreased phosphorylation of FoxO3α and Akt. FoxO3α silencing decreased hypoxia-induced autophagy and the resultant apoptosis. Furthermore, treatment with 3-Methyladenine (10 mg/kg/day) improved the endothelial-dependent diastolic function of coronary artery in rats with myocardial infarction. These results indicated that hypoxia-induced autophagy formation in CMECs is mediated by FoxO3α and contributes to hypoxic injury of hearts.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Microvascular Research - Volume 104, March 2016, Pages 23-31
نویسندگان
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