当前位置： SCI文献检索 > EUROPEAN JOURNAL OF PHARMACOLOGY期刊下所有文献 > Epigallocatechin-3-gallate ameliorates hypoxia-induced pulmonary vascular remodeling by promoting mitofusin-2-mediated mitochondrial fusion.

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

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% 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 (50μM) 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.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Zhu TT,Zhang WF,Luo P,He F,Ge XY,Zhang Z,Hu CP

doi

10.1016/j.ejphar.2017.05.003

subject

Has Abstract

pub_date

2017-08-15 00:00:00

pages

42-51

eissn

0014-2999

issn

1879-0712

pii

S0014-2999(17)30306-0

journal_volume

809

pub_type

杂志文章

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