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Epigallocatechin-3-gallate ameliorates hypoxia-induced pulmonary vascular remodeling by promoting mitofusin-2-mediated mitochondrial fusion.
- Source :
-
European journal of pharmacology [Eur J Pharmacol] 2017 Aug 15; Vol. 809, pp. 42-51. Date of Electronic Publication: 2017 May 03. - Publication Year :
- 2017
-
Abstract
- Pulmonary hypertension (PH) mainly results from excessive proliferation of pulmonary artery smooth muscle cells (PASMCs) and displays mitochondrial abnormalities such as mitochondrial fragmentation. Epigallocatechin-3-gallate (EGCG), an efficient antiproliferative compound in green tea, has recently been demonstrated to inhibit PASMCs proliferation. However, the pre-clinical issues as to whether EGCG attenuates PH and the underlying mechanisms have yet to be addressed. The present study was undertaken to investigate the therapeutic effects of EGCG on PH and its effects on mitochondrial fragmentation in PASMCs. Rats exposed to hypoxia (10% O <subscript>2</subscript> , 3 weeks) developed PH. EGCG (50, 100 or 200mg/kg/d, i.g.) dose-dependently attenuated right ventricular systolic pressure, pulmonary vascular remodeling and right ventricular hypertrophy, increased expression of mitochondrial fusion protein - mitofusin-2 (MFN-2), and promoted mitochondrial fusion as evidenced by decreased number and volume of mitochondria in PASMCs of pulmonary arteries. Notably, EGCG (50μM) downregulated hypoxia-induced (3% O <subscript>2</subscript> , 48h) PASMCs mitochondrial fragmentation and inhibited PASMCs proliferation via KLF-4/MFN-2/p-Erk signaling pathway. Collectively, our data demonstrated that EGCG exerts antiproliferative effects via regulating mitochondrial fragmentation of PASMCs and EGCG holds the promise as a drug against PH.<br /> (Copyright © 2017. Published by Elsevier B.V.)
- Subjects :
- Animals
Catechin pharmacology
Cell Proliferation drug effects
Dose-Response Relationship, Drug
GTP Phosphohydrolases
Kruppel-Like Factor 4
Kruppel-Like Transcription Factors metabolism
Male
Mitogen-Activated Protein Kinase 1 metabolism
Mitogen-Activated Protein Kinase 3 metabolism
Myocytes, Smooth Muscle drug effects
Myocytes, Smooth Muscle pathology
Pulmonary Artery metabolism
Rats
Rats, Sprague-Dawley
Signal Transduction drug effects
Up-Regulation drug effects
Catechin analogs & derivatives
Hypoxia pathology
Membrane Proteins metabolism
Mitochondrial Dynamics drug effects
Mitochondrial Proteins metabolism
Pulmonary Artery drug effects
Pulmonary Artery pathology
Vascular Remodeling drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0712
- Volume :
- 809
- Database :
- MEDLINE
- Journal :
- European journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 28478070
- Full Text :
- https://doi.org/10.1016/j.ejphar.2017.05.003