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Mitochondrial Division Inhibitor Mdivi-1 Ameliorates Angiotensin II-induced Endothelial Dysfunction

Mitochondrial Division Inhibitor Mdivi-1 Ameliorates Angiotensin II-induced Endothelial Dysfunction

Yu Chen, Jing-Rong Lin, Ping-Jin Gao

Sheng Li Xue Bao. 2016 Oct 25;68(5):669-676.

PMID: 27778033

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 (AngII) 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 AngII. The HUVECs were treated with AngII alone or in combination with Mdivi-1. Western blot was used to detect protein expressions of Drp1, endothelial nitric oxide synthase (eNOS) and apoptosis-related enzymes. MitoTracker 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, AngII (1 × 10-7 mol/L, 12 h) treatment significantly upregulated the expression of Drp1 followed by increased apoptosis and decreased eNOS expression. The treatment of AngII 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 AngII-induced endothelial dysfunction, as shown by increased mitochondrial membrane potential and eNOS expression, reduced ROS level, decreased apoptosis and migration ability. Taking together, our data suggest that inhibition of Drp1 with Mdivi-1 can restore AngII-induced endothelial dysfunction.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP338967876-B	Mitochondrial Division Inhibitor, mdivi-1 - CAS 338967-87-6		338967-87-6	Price
AP4091990	2ʹ,7ʹ-Dichlorofluorescin Diacetate - CAS 4091-99-0		4091-99-0	Price

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