title: 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.
authors.affiliation: Department of Pharmacology, School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, China.
authors.forename: Xiang-Yun
authors.initials: XY
authors.lastname: Gai
authors.forename: Feng
authors.initials: F
authors.lastname: Tang
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.forename: Ke-Wu
authors.initials: KW
authors.lastname: Zeng
authors.forename: Sheng-Lan
authors.initials: SL
authors.lastname: Wang
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Wang
authors.forename: Ta-Na
authors.initials: TN
authors.lastname: Wuren
authors.forename: Dian-Xiang
authors.initials: DX
authors.lastname: Lu
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.forename: Ri-Li
authors.initials: RL
authors.lastname: Ge
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D015687:Cell Hypoxia / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D006027:Glycosides / Q000494:pharmacology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000201:enzymology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011651:Pulmonary Artery / Q000166:cytology* / Q000201:enzymology; D017208:Rats, Wistar; D066253:Vascular Remodeling / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
chemical_list: C494828:Bax protein, rat; C491898:Fas protein, rat; D006027:Glycosides; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D019014:fas Receptor; D053148:Caspase 3; C060297:echinacoside