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Biochem Biophys Res Commun ; 465(1): 101-7, 2015 Sep 11.
Article in English | MEDLINE | ID: mdl-26239661

ABSTRACT

Angiotensin II (Ang II) has been shown to activate multiple downstream pathways resulting in endothelial dysfunction and oxidative stress. Baicalin, a natural flavone, exerts anti-oxidant and anti-apoptotic effects in cardiovascular diseases. In the present study, we hypothesized that baicalin has beneficial effects in Ang II-induced endothelial cells injury. Here, we shown that baicalin improved endothelial fuction impaired by Ang II through promoting endothelial-dependent vasodilation and suppressing the apoptosis of HUVECs in which baicalin decreased the expression of bax and cleaved caspase-3, and increased bcl-2 expression. Additionally, baicalin significantly conversed Ang II to angiotensin-1-7 [Ang-(1-7)] by activating angiotensin-converting enzyme 2 (ACE2) and Mas receptor mRNA expression and protein expression. Moreover, treatment with baicalin significantly reduced cell oxidative damage induced by Ang II through MDA/ROS decrease and NO/T-AOC increase. This antioxidant capacity was related to the increases of PI3K, phosphor-AKT (Ser-473) and phosphor-eNOS (Ser-1177). In conclusion, our results implicate that baicalin could protect endothelial cells from Ang II-induced endothelial dysfunction and oxidative stress via modulating the expression of bax, bcl-2 and cleaved caspase-3, activating ACE2/Ang-(1-7)/Mas axis and up-regulating PI3K/AKT/eNOS pathway.


Subject(s)
Angiotensin II/pharmacology , Caspase 3/metabolism , Flavonoids/pharmacology , Human Umbilical Vein Endothelial Cells/drug effects , Proto-Oncogene Proteins c-bcl-2/metabolism , bcl-2-Associated X Protein/metabolism , Angiotensin I/agonists , Angiotensin I/metabolism , Angiotensin II/metabolism , Angiotensin-Converting Enzyme 2 , Animals , Aorta, Thoracic/drug effects , Aorta, Thoracic/metabolism , Apoptosis/drug effects , Caspase 3/genetics , Gene Expression Regulation , Human Umbilical Vein Endothelial Cells/cytology , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Nitric Oxide Synthase Type III/genetics , Nitric Oxide Synthase Type III/metabolism , Oxidative Stress , Peptide Fragments/agonists , Peptide Fragments/metabolism , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/metabolism , Phosphatidylinositol 3-Kinases/genetics , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/agonists , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-bcl-2/genetics , Rats , Signal Transduction , Tissue Culture Techniques , Vasodilation/drug effects , bcl-2-Associated X Protein/antagonists & inhibitors , bcl-2-Associated X Protein/genetics
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