The Involvement of CXCR4 in the Inhibitory Effects of Salvianolic Acid B on Smooth Muscle Cell Proliferation

Abstract

CXCR4, the unique receptor for stromal cell-derived factor-1 alpha (SDF-1 alpha), has been recently implicated in the development of neoitimal formation after vascular injury in apolipoprotein E-deficient mice. In the present study we investigated a pure compound salvianolic acid B from Salvia militorrhiza, a common Chinese herbal medicine, about its inhibitory effect on rat vascular smooth muscle cells (VSMCs) for cell proliferation, CXCR4 expression, cellular migration and its related signaling activities. Our results demonstrated that SDF-1alpha-induced cell proliferation can be significantly inhibited by salvianolic acid B. The quantitative analysis by real time PCR indicated a potent inhibitory effects of salvianolic acid on CXCR4 mRNA expression. The translational activities of cell proliferation-related proteins, such as Raf-1, MEK, ERK, CXCR4 and FAK, were all inhibited by 42%, 36%, 43%, 31% and 37%, respectively. Cell migration potentiated by SDF-1alpha was also attenuated by salvianolic acid B. In the aspect of apoptosis, salvianolic acid B can induce VSMCs apoptosis via cpspase 3 up-regulation and Bcl-2 down-regulation. In summary, considering the effects on cell proliferation and migration, salvianolic acid B may provide an alternative therapeutic remedy in preventing balloon injury-induced neoitimal formation.