Abstract
Salvianolic acid B (SalB) is a bioactive component in Salvia miltiorrhiza, which is widely used as a traditional oriental medicine for treatment of cardiovascular disorders. As it is known to have cardioprotective effects and anti-inflammatory activities, it has been used for treatment of several vascular diseases. However, the precise mechanism of SalB at the transcriptional level has not so far been determined. In this study, we investigated target genes of SalB in human umbilical vein endothelial cells (HUVECs) by microarray gene expression profiling that allows a global view of gene expression. Among more than 40,000 genes investigated, 140 genes were up-regulated more than 1.7-fold, while 167 genes were down-regulated with altered expression levels of 2-fold. According to their functional characteristics, genes were classified into seven categories. We also showed the distribution of functional groups of target genes in SalB-treated HUVECs. Furthermore, cardiovascular disease-related genes, including PDGS2, TNFSF12, and IFNG, were also altered by SalB. These results suggest that SalB may exert a vasculoprotective effect through transcriptional change of inflammatory genes. In conclusion, our data suggest that these changes in gene expression mediate the anti-inflammatory activities of SalB on vasculopathy.
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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).
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).
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).
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).
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).
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. Chin. J. Integr. Med. 5, 61–64 (2007).
Liu, C.L. et al. Salvianolic acid B inhibits hydrogen peroxide-induced endothelial cell apoptosis through regulating PI3K/Akt signaling. PLoS One 2, e1321 (2007).
Tian, T. & Xu, L.M. Effects of Salviae miltiorrhizae and salvianolic acid B on microcirculation of liver in mice with portal hypertension. Chin. J. Integr. Med. 7, 151–156 (2009).
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).
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).
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).
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).
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).
Zhang, H.S. & Wang, S.Q. Salvianolic acid B from Salvia miltiorrhiza inhibits tumor necrosis factor-alpha (TNF-alpha)-induced MMP-2 upregulation in human aortic smooth muscle cells via suppression of NAD(P)H oxidase-derived reactive oxygen species. J. Mol. Cell. Cardiol. 41, 138–148 (2006).
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).
Sumpio, B.E., Riley, J.T. & Dardik, A. Cells in focus: endothelial cell. Int. J. Biochem. Cell. Biol. 34, 1508–1512 (2002).
Fonseca, V., Desouza, C., Asnani, S. & Jialal, I. Nontraditional risk factors for cardiovascular disease in diabetes. Endocr. Rev. 25, 153–175 (2004).
Libby, P. Inflammation in atherosclerosis. Nature 420, 868–874 (2002).
Dandona, P., Aljada, A., Chaudhuri, A. & Bandyopadhyay, A. The potential influence of inflammation and insulin resistance on the pathogenesis and treatment of atherosclerosis-related complications in type 2 diabetes. J. Clin. Endocrinol. Metab. 88, 2422–2429 (2003).
Cotran, R.S. & Pober, J.S. Cytokine-endothelial interactions in inflammation, immunity, and vascular injury. J. Am. Soc. Nephrol. 1, 225–235 (1990).
Kofler, S., Nickel, T. & Weis, M. Role of cytokines in cardiovascular diseases: a focus on endothelial responses to inflammation. Clin. Sci. (Lond) 108, 205–213 (2005).
Trevino, V., Falciani, F. & Barrera-Saldana, H.A. DNA microarrays: a powerful genomic tool for biomedical and clinical research. Mol. Med. 13, 527–541 (2007).
Archacki, S.R. & Wang, Q.K. Microarray analysis of cardiovascular diseases. Methods Mol. Med. 129, 1–13 (2006).
Hiltunen, M.O. et al. Changes in gene expression in atherosclerotic plaques analyzed using DNA array. Atherosclerosis 165, 23–32 (2002).
Libby, P., Ridker, P.M. & Maseri, A. Inflammation and atherosclerosis. Circulation 105, 1135–1143 (2002).
Esposito, K. et al. Inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans: role of oxidative stress. Circulation 106, 2067–2072 (2002).
Yuuki, T. et al. Inflammatory cytokines in vitreous fluid and serum of patients with diabetic vitreoretinopathy. J. Diabetes. Complications 15, 257–259 (2001).
Bishop-Bailey, D., Mitchell, J.A. & Warner, T.D. COX-2 in cardiovascular disease. Arterioscler Thromb. Vasc. Biol. 26, 956–958 (2006).
Cipollone, F. & Fazia, M.L. Cyclooxygenase-2 inhibition: vascular inflammation and cardiovascular risk. Curr. Atheroscler Rep. 8, 245–251 (2006).
Chenevard, R. et al. Selective COX-2 inhibition improves endothelial function in coronary artery disease. Circulation 107, 405–409 (2003).
Kellogg, A.P., Converso, K., Wiggin, T., Stevens, M. & Pop-Busui, R. Effects of cyclooxygenase-2 gene inactivation on cardiac autonomic and left ventricular function in experimental diabetes. Am. J. Physiol. Heart Circ. Physiol. 296, H453–461 (2009).
Saas, P. et al. TWEAK stimulation of astrocytes and the proinflammatory consequences. Glia 32, 102–107 (2000).
Campbell, S., Michaelson, J., Burkly, L. & Putterman, C. The role of TWEAK/Fn14 in the pathogenesis of inflammation and systemic autoimmunity. Front Biosci. 9, 2273–2284 (2004).
Chicheportiche, Y. et al. TWEAK, a new secreted ligand in the tumor necrosis factor family that weakly induces apoptosis. J. Biol. Chem. 272, 32401–32410 (1997).
Ortiz, A. et al. Considering TWEAK as a target for therapy in renal and vascular injury. Cytokine Growth. Factor. Rev. 20, 251–258 (2009).
Ebihara, N. et al. Proinflammatory effect of TWEAK/Fn14 interaction in human retinal pigment epithelial cells. Curr. Eye. Res. 34, 836–844 (2009).
Kim, S.H. et al. TWEAK can induce pro-inflammatory cytokines and matrix metalloproteinase-9 in macrophages. Circ. J. 68, 396–399 (2004).
Gajewski, T.F., Goldwasser, E. & Fitch, F.W. Antiproliferative effect of IFN-gamma in immune regulation. II. IFN-gamma inhibits the proliferation of murine bone marrow cells stimulated with IL-3, IL-4, or granulocyte-macrophage colony-stimulating factor. J. Immunol. 141, 2635–2642 (1988).
Munro, J.M., Pober, J.S. & Cotran, R.S. Tumor necrosis factor and interferon-gamma induce distinct patterns of endothelial activation and associated leukocyte accumulation in skin of Papio anubis. Am. J. Pathol. 135, 121–133 (1989).
Li, J.H. et al. Interferon-gamma augments CD95 (APO-1/Fas) and pro-caspase-8 expression and sensitizes human vascular endothelial cells to CD95-mediated apoptosis. Am. J. Pathol. 161, 1485–1495 (2002).
Leeuwenberg, J.F., von Asmuth, E.J., Jeunhomme, T.M. & Buurman, W.A. IFN-gamma regulates the expression of the adhesion molecule ELAM-1 and IL-6 production by human endothelial cells in vitro. J. Immunol. 145, 2110–2114 (1990).
Lombardi, A. et al. Molecular mechanisms underlying the pro-inflammatory synergistic effect of tumor necrosis factor alpha and interferon gamma in human microvascular endothelium. Eur. J. Cell. Biol. 88, 731–742 (2009).
Lee, S.H. et al. Identification of atherosclerosis related gene expression profiles by treatment of Benzo(a) pyrene in human umbilical vein endothelial cells. Mol. Cell. Toxicol. 5, 113–119 (2009).
Park, Y.S. et al. Acrolein induces cyclooxygenase-2 and prostaglandin production in human umbilical vein endothelial cells: roles of p38 MAP kinase. Arterioscler Thromb. Vasc. Biol. 27, 1319–1325 (2007).
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Yang, H., Lee, S.E., Ryu, D.S. 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). https://doi.org/10.1007/s13206-011-5108-1
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DOI: https://doi.org/10.1007/s13206-011-5108-1