Mitochondrial division inhibitor Mdivi-1 ameliorates angiotensin II-induced endothelial dysfunction.
- Author:
Yu CHEN
1
;
Jing-Rong LIN
2
;
Ping-Jin GAO
1
Author Information
1. Laboratory of Vascular Biology, Institute of Health Science, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), University of Chinese Academy of Sciences, Shanghai 200025, China.
2. State Key Laboratory of Medical Genomics and Shanghai Key Laboratory of Vascular Biology at Ruijin Hospital and Shanghai Institute of Hypertension, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. jingrong.lin@163.com.
- Publication Type:Journal Article
- MeSH:
Angiotensin II;
Apoptosis;
Cells, Cultured;
Endothelial Cells;
Fluoresceins;
Humans;
Membrane Potential, Mitochondrial;
Microtubule-Associated Proteins;
Mitochondria;
Mitochondrial Proteins;
Nitric Oxide Synthase Type III;
Quinazolinones
- From:
Acta Physiologica Sinica
2016;68(5):669-676
- CountryChina
- Language:English
-
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 × 10mol/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.
