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Antiproliferative effect of echinacoside on rat pulmonary artery smooth muscle cells under hypoxia.

Abstract
The main purpose of this study is to evaluate the effect of echinacoside (ECH) on hypoxia-induced proliferation of rat pulmonary artery smooth muscle cells (PASMCs) and the underlying mechanism. PASMCs were incubated under normoxia (nor), hypoxia (hyp), hypoxia + 0.35 mM ECH (hyp + ECH0.35), or hypoxia + 0.4 mM ECH (hyp + ECH0.4) for 24 h. Cell viability was assessed by MTS assays. The morphology of apoptosis was observed by DAPI staining, and apoptosis was quantified by flow cytometric analysis. Caspase-3 activity was determined by immunohistochemistry and real-time PCR, and the expressions of HIF-1α, Bax, Bcl-2, and Fas were determined by real-time PCR. Hypoxia induced significant proliferation of PASMCs, which could be inhibited by ECH in a concentration-dependent manner. This was associated with apoptosis of PASMCs. Z-DEVD-FMK could partly reduce the suppression effect of ECH; protein and gene expression of caspase-3 were significantly higher in the hyp + ECH0.4 and hyp + ECH0.35 groups. ECH significantly increased the expressions of Bax and Fas, but decreased the expressions of Bcl-2 and HIF-1α. ECH could inhibit hypoxia-induced proliferation of rat PASMCs, which is associated with apoptosis of PASMCs and improvement of hypoxia. ECH might be a potential agent for prevention and treatment of hypoxia-induced PAH.
AuthorsXiang-Yun Gai, Feng Tang, Jing Ma, Ke-Wu Zeng, Sheng-Lan Wang, Ya-Ping Wang, Ta-Na Wuren, Dian-Xiang Lu, Yi Zhou, Ri-Li Ge
JournalJournal of pharmacological sciences (J Pharmacol Sci) Vol. 126 Issue 2 Pg. 155-63 ( 2014) ISSN: 1347-8648 [Electronic] Japan
PMID25341567 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Bax protein, rat
  • Fas protein, rat
  • Glycosides
  • Hif1a protein, rat
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • fas Receptor
  • Caspase 3
  • echinacoside
Topics
  • Animals
  • Apoptosis (drug effects)
  • Caspase 3 (genetics, metabolism)
  • Cell Hypoxia (physiology)
  • Cell Proliferation (drug effects)
  • Cells, Cultured
  • Depression, Chemical
  • Dose-Response Relationship, Drug
  • Gene Expression (drug effects)
  • Glycosides (pharmacology)
  • Hypoxia-Inducible Factor 1, alpha Subunit (genetics, metabolism)
  • Male
  • Muscle, Smooth, Vascular (cytology, enzymology)
  • Proto-Oncogene Proteins c-bcl-2 (metabolism)
  • Pulmonary Artery (cytology, enzymology)
  • Rats, Wistar
  • Vascular Remodeling (drug effects)
  • bcl-2-Associated X Protein (genetics, metabolism)
  • fas Receptor (metabolism)

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