Jinghan Lin1, Yi Xu1, Tingting Zhao1, Lina Sun1, Meimei Yang1, Tingjiao Liu1, Hui Sun1, Liming Zhang2. 1. Department of Neurology, The First Affiliated Hospital of Harbin Medical University, 23 Post Street, Harbin 150001, PR China. 2. Department of Neurology, The First Affiliated Hospital of Harbin Medical University, 23 Post Street, Harbin 150001, PR China. Electronic address: zfx0001@126.com.
Abstract
PURPOSE: Genistein, as a protein tyrosine kinase inhibitor, has been shown to possess anti-atherosclerotic effects. Since the smooth muscle cell-derived foam cells are key components of atherosclerotic plaques. The aim of this study is to investigate the influence of genistein on foam cell transformation from vascular smooth muscle cells and possible mechanisms contributing to these effects. METHODS AND RESULTS: Vascular smooth muscle cells exposed to ox-LDL developed into foam cell, as demonstrated by Oil Red O staining and cholesterol content analysis. Ox-LDL induced phenotype transformation of smooth muscle cells, decreased expression of α-actin and increased expression of CD68 (a specific marker for monocytes, can also function as a subtype of scavenger receptors). The expression of scavenger receptors CD36 and LOX-1 was measured, and their role in foam cell formation in the presence of genistein, daidzein (a structurally similar analogue of genistein) and herbimycin A (a commonly tyrosine kinase inhibitor). The results showed that foam cell formation was markedly reduced by genistein and herbimycin A, as well as the expression of CD68, CD36 and LOX-1. However, daidzein had no such effect. In addition, genistein-induced down-regulation of CD68, CD36 and LOX-1 could be reversed by sodium orthovanadate (a membrane-permeable protein tyrosine phosphatase inhibitor). CONCLUSION: The results showed that ox-LDL induce smooth muscle cell-derived foam cell formation and transform the phenotype of smooth muscle cell. While tyrosine kinase inhibitor, genistein could suppress smooth muscle cell-derived foam cell formation through inhibiting the protein expressions of CD68, CD36 and LOX-1.
PURPOSE:Genistein, as a protein tyrosine kinase inhibitor, has been shown to possess anti-atherosclerotic effects. Since the smooth muscle cell-derived foam cells are key components of atherosclerotic plaques. The aim of this study is to investigate the influence of genistein on foam cell transformation from vascular smooth muscle cells and possible mechanisms contributing to these effects. METHODS AND RESULTS: Vascular smooth muscle cells exposed to ox-LDL developed into foam cell, as demonstrated by Oil Red O staining and cholesterol content analysis. Ox-LDL induced phenotype transformation of smooth muscle cells, decreased expression of α-actin and increased expression of CD68 (a specific marker for monocytes, can also function as a subtype of scavenger receptors). The expression of scavenger receptors CD36 and LOX-1 was measured, and their role in foam cell formation in the presence of genistein, daidzein (a structurally similar analogue of genistein) and herbimycin A (a commonly tyrosine kinase inhibitor). The results showed that foam cell formation was markedly reduced by genistein and herbimycin A, as well as the expression of CD68, CD36 and LOX-1. However, daidzein had no such effect. In addition, genistein-induced down-regulation of CD68, CD36 and LOX-1 could be reversed by sodium orthovanadate (a membrane-permeable protein tyrosine phosphatase inhibitor). CONCLUSION: The results showed that ox-LDL induce smooth muscle cell-derived foam cell formation and transform the phenotype of smooth muscle cell. While tyrosine kinase inhibitor, genistein could suppress smooth muscle cell-derived foam cell formation through inhibiting the protein expressions of CD68, CD36 and LOX-1.