Epigallocatechin-3-gallate ameliorates hypoxia-induced pulmonary vascular remodeling by promoting mitofusin-2-mediated mitochondrial fusion.

Authors: Zhu, Tian-Tian  Zhang, Wei-Fang  Luo, Ping  He, Fang  Ge, Xiao-Yue  Zhang, Zheng  Hu, Chang-Ping 
Citation: Zhu TT, etal., Eur J Pharmacol. 2017 Aug 15;809:42-51. doi: 10.1016/j.ejphar.2017.05.003. Epub 2017 May 3.
Pubmed: (View Article at PubMed) PMID:28478070
DOI: Full-text: DOI:10.1016/j.ejphar.2017.05.003

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% O2, 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 (50┬ÁM) downregulated hypoxia-induced (3% O2, 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.

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CRRD Object Information
CRRD ID: 12910733
Created: 2017-06-22
Species: All species
Last Modified: 2017-06-22
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.