Skip to main content
Log in

An integrated analysis of microRNA and mRNA expression in salvianolic acid B-treated human umbilical vein endothelial cells

  • Original Paper
  • Published:
Molecular & Cellular Toxicology Aims and scope Submit manuscript

Abstract

MicroRNAs (miRNAs) are a class of small noncoding RNAs, producing transcripts of about 22 nucleotides in length. miRNAs usually function as antisense regulators of other RNAs by degrading their targets. Recently, miRNAs have emerged as interesting new drug targets due to their regulatory role in essential biological processes. Salvianolic acid B (SalB) is one of the major pharmacologically active ingredients of Salvia miltiorrhiza, a traditional oriental medicine for treatment of cardiovascular disorders. In this study, we determined whether miRNAs play a role in regulation of various gene expression responses to SalB in human umbilical vein endothelial cells (HUVECs). We used the microarray approach to evaluate levels of both miRNA and mRNA, and found that 171 miRNAs were differentially expressed in SalB-treated HUVECs. We additionally identified 848 messenger RNAs (mRNAs) that are anti-correlated with the miRNAs expression. The Gene Ontology (GO) term enrichment was analyzed for identification of biological processes of target genes affected by differential expression of miRNA. Among 848 genes investigated, cardiovascular diseaserelated genes were selected in SalB-treated HUVECs. These results suggest that SalB may modulate miRNA and their target gene expression in order to exert vascular protective effects in human endothelial cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Filipowicz, W., Bhattacharyya, S. N. & Sonenberg, N. Mechanisms of post-transcriptional regulation by micro RNAs: are the answers in sight? Nat Rev Genet 9:102–114 (2008).

    Article  PubMed  CAS  Google Scholar 

  2. Urbich, C., Kuehbacher, A. & Dimmeler, S. Role of microRNAs in vascular diseases, inflammation, and angiogenesis. Cardiovasc Res 79:581–588 (2008).

    Article  PubMed  CAS  Google Scholar 

  3. Wang, S. X., Hu, L. M., Gao, X. M., Guo, H. & Fan, G. W. Anti-inflammatory activity of salvianolic acid B in microglia contributes to its neuroprotective effect. Neurochem Res 35:1029–1037 (2010).

    Article  PubMed  CAS  Google Scholar 

  4. Zhou, Z., Liu, Y., Miao, A. D. & Wang, S. Q. Salvianolic acid B attenuates plasminogen activator inhibitor type 1 production in TNF-alpha treated human umbilical vein endothelial cells. J Cell Biochem 96: 109–116 (2005).

    Article  PubMed  CAS  Google Scholar 

  5. Chen, Y. L. et al. Salvianolic acid B attenuates cyclooxygenase-2 expression in vitro in LPS-treated human aortic smooth muscle cells and in vivo in the apolipoprotein-E-deficient mouse aorta. J Cell Biochem 98: 618–631 (2006).

    Article  PubMed  CAS  Google Scholar 

  6. Liu, C. S., Chen, N. H. & Zhang, J. T. Protection of PC12 cells from hydrogen peroxide-induced cytotoxicity by salvianolic acid B, a new compound isolated from Radix Salviae miltiorrhizae. Phytomedicine 14: 492–497 (2007).

    Article  PubMed  CAS  Google Scholar 

  7. Lam, F. F., Yeung, J. H., Kwan, Y. W., Chan, K. M. & Or, P. M. Salvianolic acid B, an aqueous component of danshen (Salvia miltiorrhiza), relaxes rat coronary artery by inhibition of calcium channels. Eur J Pharmacol 553:240–245 (2006).

    Article  PubMed  CAS  Google Scholar 

  8. Zhou, Y., Gu, J. & Xu, L. M. Effect and mechanism of salvianolic acid B in attenuating elevated portal pressure in a rat model of portal hypertension induced by endothelin-1. Zhong Xi Yi Jie He Xue Bao 5:61–64 (2007).

    Article  PubMed  CAS  Google Scholar 

  9. Lin, S. J. et al. Salvianolic acid B attenuates MMP-2 and MMP-9 expression in vivo in apolipoprotein-Edeficient mouse aorta and in vitro in LPS-treated human aortic smooth muscle cells. J Cell Biochem 100:372–384 (2007).

    Article  PubMed  CAS  Google Scholar 

  10. Chen, Y. H. et al. Salvianolic acid B attenuates VCAM-1 and ICAM-1 expression in TNF-alpha-treated human aortic endothelial cells. J Cell Biochem 82:512–521 (2001).

    Article  PubMed  CAS  Google Scholar 

  11. Yan, Q., Yao-Cheng, R., Li, Z., Tie-Jun, L. & Wei-Dong, Z. VEGF induced hyperpermeability in bovine aortic endothelial cell and inhibitory effect of salvianolic acid B. Acta Pharmacologica Sinica 22:117–120 (2001).

    Google Scholar 

  12. Ding, M., Ye, T. X., Zhao, G. R., Yuan, Y. J. & Guo, Z. X. Aqueous extract of Salvia miltiorrhiza attenuates increased endothelial permeability induced by tumor necrosis factor-alpha. Int Immunopharmacol 5:1641–1651 (2005).

    Article  PubMed  CAS  Google Scholar 

  13. Wu, H. L. et al. Salvianolic acid B protects human endothelial cells from oxidative stress damage: a possible protective role of glucose-regulated protein 78 induction. Cardiovasc Res 81:148–158 (2009).

    Article  PubMed  CAS  Google Scholar 

  14. Zhang, J., Zhao, G., Liu, J. & Ji, X. Protection of salvianolic acid B for human endothelial cells against hydrogen peroxide-induced oxidative damage. Transactions of Tianjin University 15:434–439 (2009).

    Article  CAS  Google Scholar 

  15. Chen, S. C., Lin, Y. L., Huang, B., Wang, D. L. & Cheng, J. J. Salvianolic acid B suppresses IFN-gamma-induced JAK/STAT1 activation in endothelial cells. Thromb Res 128:560–564 (2011).

    Article  PubMed  CAS  Google Scholar 

  16. Zhao, J. F. et al. Effect of salvianolic acid B on Smad3 expression in hepatic stellate cells. Hepatobiliary Pancreat Dis Int 3:102–105 (2004).

    PubMed  CAS  Google Scholar 

  17. Dennis, G., Jr. et al. DAVID: Database for Annotation, Visualization, and Integrated Discovery. Genome Biol 4:P3 (2003).

    Article  PubMed  Google Scholar 

  18. Sumpio, B. E., Riley, J. T. & Dardik, A. Cells in focus: endothelial cell. Int J Biochem Cell Biol 34:1508–1512 (2002).

    Article  PubMed  CAS  Google Scholar 

  19. Wang, Q. L., Wu, Q., Tao, Y. Y., Liu, C. H. & El-Nezami, H. Salvianolic acid B modulates the expression of drug-metabolizing enzymes in HepG2 cells. Hepatobiliary Pancreat Dis Int 10:502–508 (2011).

    Article  PubMed  CAS  Google Scholar 

  20. Wu, Y. P. et al. Salvianolic acid B inhibits platelet adhesion under conditions of flow by a mechanism involving the collagen receptor alpha2beta1. Thromb Res 123:298–305 (2008).

    Article  PubMed  CAS  Google Scholar 

  21. Xu, L. L. et al. Cardio-Protection of Salvianolic Acid B through Inhibition of Apoptosis Network. PLoS One 6:e24036 (2011).

    Article  PubMed  CAS  Google Scholar 

  22. Yang, X. Y. et al. Salvianolic acid A protects against vascular endothelial dysfunction in high-fat diet fed and streptozotocin-induced diabetic rats. J Asian Nat Prod Res 13:884–894 (2011).

    Article  PubMed  CAS  Google Scholar 

  23. Ness, S. A. Microarray analysis: basic strategies for successful experiments. Mol Biotechnol 36:205–219 (2007).

    Article  PubMed  CAS  Google Scholar 

  24. Lim, L. P. et al. Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature 433:769–773 (2005).

    Article  PubMed  CAS  Google Scholar 

  25. Lorenzen, J., Kumarswamy, R., Dangwal, S. & Thum, T. MicroRNAs in diabetes and diabetes-associated complications. RNA Biol 9:820–827(2012).

    Article  PubMed  CAS  Google Scholar 

  26. Lee, S. E. et al. MicroRNA and gene expression analysis of melatonin-exposed human breast cancer cell lines indicating involvement of the anticancer effect. J Pineal Res 51:345–352 (2011).

    Article  PubMed  CAS  Google Scholar 

  27. Zernecke, A. MicroRNAs in the regulation of immune cell functions — implications for atherosclerotic vascular disease. Thromb Haemost 107:626–633 (2012).

    Article  PubMed  CAS  Google Scholar 

  28. Zampetaki, A. & Mayr, M. MicroRNAs in vascular and metabolic disease. Circ Res 110:508–522 (2012).

    Article  PubMed  CAS  Google Scholar 

  29. Harris, T. A., Yamakuchi, M., Ferlito, M., Mendell, J. T. & Lowenstein, C. J. MicroRNA-126 regulates endothelial expression of vascular cell adhesion molecule 1. Proc Natl Acad Sci USA 105:1516–1521 (2008).

    Article  PubMed  CAS  Google Scholar 

  30. Lee, S. E. et al. Uncaria rhynchophylla induces heme oxygenase-1 as a cytoprotective effect in RAW 264.7 macrophages. Mol. Cell. Toxicol. 6:33–40 (2010).

    Article  CAS  Google Scholar 

  31. Kim, J. H. Cardiovascular Diseases and Panax ginseng: A Review on Molecular Mechanisms and Medical Applications. J. Ginseng Res. 36:16–26 (2012).

    Article  CAS  Google Scholar 

  32. Choi, K. S. et al. Inhibition of Hydrogen Sulfide-induced Angiogenesis and Inflammation in Vascular Endothelial Cells: Potential Mechanisms of Gastric Cancer Prevention by Korean Red Ginseng. J. Ginseng Res. 36:135–145 (2012).

    Article  Google Scholar 

  33. Yang, F. G. et al. Effects of salvianolic acid B on cardiovascular endothelial cells and platelet activation in a rabbit model of ischemia-reperfusion. Zhong Xi Yi Jie He Xue Bao 6:1250–1254 (2008).

    Article  PubMed  CAS  Google Scholar 

  34. Arola-Arnal, A. & Blade, C. Proanthocyanidins modulate microRNA expression in human HepG2 cells. PLoS One 6:e25982 (2011).

    Article  PubMed  CAS  Google Scholar 

  35. Joven, J. et al. Plant-derived polyphenols regulate expression of miRNA paralogs miR-103/107 and miR-122 and prevent diet-induced fatty liver disease in hyperlipidemic mice. Biochim Biophys Acta 1820:894–899 (2012).

    Article  PubMed  CAS  Google Scholar 

  36. Milenkovic, D. et al. Modulation of miRNA expression by dietary polyphenols in apoE deficient mice: a new mechanism of the action of polyphenols. PLoS One 7:e29837 (2012).

    Article  PubMed  CAS  Google Scholar 

  37. Wang, H., Bian, S. & Yang, C. S. Green tea polyphenol EGCG suppresses lung cancer cell growth through upregulating miR-210 expression caused by stabilizing HIF-1alpha. Carcinogenesis 32:1881–1889 (2011).

    Article  PubMed  CAS  Google Scholar 

  38. Wen, X. Y. et al. Ellagitannin (BJA3121), an anti-proliferative natural polyphenol compound, can regulate the expression of MiRNAs in HepG2 cancer cells. Phytother Res 23:778–784 (2009).

    Article  PubMed  CAS  Google Scholar 

  39. Yang, H. et al. Expression profile analysis of human umbilical vein endothelial cells treated with salvianolic acid B from Salvia miltiorrhiza. BioChip J. 5:47–55 (2011).

    Article  Google Scholar 

  40. Lee, S. E. et al. Methylglyoxal-mediated alteration of gene expression in human endothelial cells. BioChip J. 5:220–228 (2011).

    Article  CAS  Google Scholar 

  41. Yang, H. et al. Up-regulation of Heme Oxygenase-1 by Korean Red Ginseng Water Extract as a Cytoprotective Effect in Human Endothelial Cells. J. Ginseng Res. 35:352–359 (2011).

    Article  CAS  Google Scholar 

  42. Lee, S. E. et al. Induction of Heme Oxygenase-1 Inhibits Cell Death in Crotonaldehyde-Stimulated HepG2 Cells via the PKC-delta-p38-Nrf2 Pathway. PLoS One 7:e41676 (2012).

    Article  PubMed  CAS  Google Scholar 

  43. Lee, S. E. et al. Genome-wide profiling in melatoninexposed human breast cancer cell lines identifies differentially methylated genes involved in the anticancer effect of melatonin. J Pineal Res 54:80–88 (2012).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yong Seek Park.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yang, H., Lee, S.E., Kim, GD. et al. An integrated analysis of microRNA and mRNA expression in salvianolic acid B-treated human umbilical vein endothelial cells. Mol. Cell. Toxicol. 9, 1–7 (2013). https://doi.org/10.1007/s13273-013-0001-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13273-013-0001-8

Keywords

Navigation