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Mitochondrial division inhibitor Mdivi-1 ameliorates angiotensin Ⅱ-induced endothelial dysfunction
Author(s): 
Pages: 669-676
Year: Issue:  5
Journal: Acta Physiologica Sinica

Keyword:  angiotensin Ⅱhuman umbilical vascular endothelial cellsMdivi-1endothelial dysfunctionreactive oxygen species;
Abstract: Mitochondrial fission can occur via activation of dynamin-related protein 1(Drp1), which participates in the mitochondrial membrane scission process. The present study was designed to investigate the effect of angiotensin II(Ang II) on mitochondrial fission and fusion in human umbilical vascular endothelial cells(HUVECs). And we further inquire into whether Mdivi-1, a newly identified pharmacological inhibitor of Drp1, can prevent endothelial dysfunction induced by Ang II. The HUVECs were treated with Ang II alone or in combination with Mdivi-1. Western blot was used to detect protein expressions of Drp1, endothelial nitric oxide synthase(e NOS) and apoptosis-related enzymes. Mito Tracker Red and JC-1 dye were used to detect mitochondrial morphology and membrane potential, respectively. DCFH-DA probe was used to access intracellular reactive oxygen species(ROS) generation. Transwell assay was used to evaluate cell migration. Annexin V/PI staining was used to assess cellular apoptosis. The results showed that, in cultured HUVECs, Ang II(1 × 10-7 mol/L, 12 h) treatment significantly upregulated the expression of Drp1 followed by increased apoptosis and decreased e NOS expression. The treatment of Ang II resulted in a change in mitochondrial morphology from elongated to uniformly punctate organelles, which was accompanied by decreased mitochondrial membrane potential. Furthermore, Mdivi-1 significantly protected against Ang II-induced endothelial dysfunction, as shown by increased mitochondrial membrane potential and e NOS expression, reduced ROS level, decreased apoptosis and migration ability. Taking together, our data suggest that inhibition of Drp1 with Mdivi-1 can restore Ang II-induced endothelial dysfunction.
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