Genistein Inhibits ox-LDL-induced VCAM-1, ICAM-1 and MCP-1 Expression of HUVECs Through Heme Oxygenase-1

• Published in: Archives of medical research 2013, Vol.44 (1), p.13-20
• Main Authors: Zhang, Hua-ping, Zheng, Feng-li, Zhao, Jia-hui, Guo, Dong-xing, Chen, Xiao-long
• Format: Article
• Language: English
• Subjects: Atherosclerosis; Cell Nucleus - drug effects; Cell Nucleus - metabolism; Cell Survival - drug effects; Chemokine CCL2 - biosynthesis; Chemokine CCL2 - genetics; Chemokine CCL2 - secretion; Down-Regulation - drug effects; Genistein; Genistein - pharmacology; Heme Oxygenase-1 - genetics; Heme Oxygenase-1 - metabolism; HO-1; Human Umbilical Vein Endothelial Cells - cytology; Human Umbilical Vein Endothelial Cells - drug effects; Human Umbilical Vein Endothelial Cells - enzymology; Human Umbilical Vein Endothelial Cells - metabolism; Humans; Inflammation; Intercellular Adhesion Molecule-1 - biosynthesis; Intercellular Adhesion Molecule-1 - genetics; Intercellular Adhesion Molecule-1 - metabolism; Internal Medicine; Lipoproteins, LDL - pharmacology; NF-E2-Related Factor 2 - metabolism; Nrf2; RNA, Messenger - genetics; RNA, Messenger - metabolism; Vascular Cell Adhesion Molecule-1 - biosynthesis; Vascular Cell Adhesion Molecule-1 - genetics; Vascular Cell Adhesion Molecule-1 - metabolism
• ISSN: 0188-4409; 1873-5487
• DOI: 10.1016/j.arcmed.2012.12.001

Background and Aims Genistein, a principal component of soybean isoflavones, plays an important role in the prevention of atherosclerosis. However, the detailed mechanisms have not been fully investigated. The aims of this study were to evaluate the anti-atherosclerotic effect and investigate potential pharmacological mechanism of genistein. Methods A model of oxidized low-density lipoprotein (ox-LDL)-induced injury in on human umbilical vein endothelial cells (HUVECs) was established to evaluate the protective role of genistein. Macrophage/monocyte chemoattractant protein-1 (MCP-1), vascular cellular adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1) secretion and their messenger RNA transcription were observed via enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase PCR (RT-PCR). Meanwhile, the study investigated the role of Nrf2/HO-1 pathway during the process. Results Pretreatment with genistein markedly reduced ox-LDL-induced MCP-1, VCAM-1 and ICAM-1 secretion and mRNA transcription, which was further decreased by the inducer of HO and reversed by the inhibitor of HO; additionally, the effects were accompanied with upregulating HO-1 mRNA and protein expression and markedly abolished with Nrf2 siRNA. Conclusions Anti-inflammatory effect of genistein on endothelial cells may be associated with the activation of Nrf2/HO-1 pathway.