Tanshinone IIA attenuates cyclic strain-induced endothelin-1 expression in human umbilical vein endothelial cells

Hong Jye Hong, Feng Lin Hsu, Shih Chang Tsai, Cheng Hsin Lin, Ju Chi Liu, Jin Jer Chen, Tzu Hurng Cheng, Paul Chan

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

1. Tanshinone IIA, one of the active components of the Radix of Salvia miltiorrhiza, is used in traditional Chinese medicine to treat cardiovascular diseases. However, the intracellular mechanism of action of tanshinone IIA remain to be determined. The aims of the present study were to test the hypothesis that tanshinone IIA alters strain-induced endothelin (ET)-1 expression and nitric oxide (NO) production, as well as to identify the putative signalling pathways involved, in human umbilical vein endothelial cells (HUVEC). 2. Cultured HUVEC were exposed to cyclic strain in the presence of 1-10μmol/L tanshinone IIA. Expression of ET-1 was examined by reverse transcription-polymerase chain reaction and ELISA. Phosphorylation of endothelial NO synthase (eNOS) and activating transcription factor (ATF) 3 was assessed by western blot analysis. 3. Tanshinone IIA (3 and 10μmol/L) inhibited strain-induced ET-1 expression. In contrast, NO production, eNOS phosphorylation and ATF3 expression were enhanced by tanshinone IIA. The eNOS inhibitor N G-nitro-l-arginine methyl ester (l-NAME; 100μmol/L), the phosphatidylinositol 3-kinase inhibitor LY294002 (5 μmol/L) and the soluble guanylyl cyclase inhibitor 1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one (ODQ; 10 μmol/L) inhibited tanshinone IIA-induced increases in ATF3 expression. Moreover, treatment of HUVEC with either an NO donor (3,3-bis [aminoethyl]-1-hydroxy-2-oxo-1-triazene; 500 μmol/L) or an ATF3 activator (carbobenzoxy-l-leucyl-l-leucyl-l-leucinal; 5μmol/L) resulted in the repression of strain-induced ET-1 expression. The inhibitory effect of tanshinone IIA on strain-induced ET-1 expression was significantly attenuated by l-NAME, ODQ and the transfection of small interfering RNA for ATF3. 4. In conclusion, tanshinone IIA inhibits strain-induced ET-1 expression by increasing NO and upregulating ATF3 in HUVEC. The present study provides important new insights into the molecular pathways that may contribute to the beneficial effects of tanshinone IIA in the cardiovascular system.

Original languageEnglish
Pages (from-to)63-68
Number of pages6
JournalClinical and Experimental Pharmacology and Physiology
Volume39
Issue number1
DOIs
Publication statusPublished - Jan 2012

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Human Umbilical Vein Endothelial Cells
Endothelin-1
Nitric Oxide
Nitric Oxide Synthase
Activating Transcription Factor 3
Triazenes
Phosphorylation
tanshinone
Phosphatidylinositol 3-Kinase
Salvia miltiorrhiza
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Nitric Oxide Donors
Nitric Oxide Synthase Type III
Chinese Traditional Medicine
Cardiovascular System
Small Interfering RNA
Reverse Transcription
Transfection
Cardiovascular Diseases
Western Blotting

Keywords

  • Activating transcription factor-3
  • Cyclic strain
  • Endothelin-1
  • Nitric oxide
  • Tanshinone IIA
  • Traditional Chinese medicine

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Pharmacology

Cite this

Tanshinone IIA attenuates cyclic strain-induced endothelin-1 expression in human umbilical vein endothelial cells. / Hong, Hong Jye; Hsu, Feng Lin; Tsai, Shih Chang; Lin, Cheng Hsin; Liu, Ju Chi; Chen, Jin Jer; Cheng, Tzu Hurng; Chan, Paul.

In: Clinical and Experimental Pharmacology and Physiology, Vol. 39, No. 1, 01.2012, p. 63-68.

Research output: Contribution to journalArticle

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AU - Hsu, Feng Lin

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AU - Lin, Cheng Hsin

AU - Liu, Ju Chi

AU - Chen, Jin Jer

AU - Cheng, Tzu Hurng

AU - Chan, Paul

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KW - Nitric oxide

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