Inhibition of PDGF beta-receptor tyrosine phosphorylation and its downstream intracellular signal transduction in rat aortic vascular smooth muscle cells by kaempferol

Kaempferol, a flavonoid present in human diet and plants, has been known to show cardiovascular protection via its anti-oxidant activity. In this Study, we have investigated the effect of kaempferol on the proliferation of primary cultured rat aortic vascular smooth muscle cells (VSMCs). Kaempferol significantly inhibited 50 ng/mL platelet-derived growth factor (PDGF)-BB-induced proliferation and [H-3]-thymidine incorporation into DNA at concentrations of 5, 20 and 50 mu M without any cytotoxicity. Kaempferol also inhibited the c-fos mRNA expression induced by PDGF-BB concentration-dependently. In addition, consistent with the inhibition of cell proliferation and c-fos mRNA expression, kaempferol inhibited the PDGF beta-receptor (RP) phosphorylation in a concentration-dependent manner. Accordingly, the downstream signal transductions of PDGF-R beta such as ERK1/2, Akt and PLC-gamma l phosphorylation were also inhibited by kaempferol in the same pattern. These findings suggest that, in addition to its anti-oxidant activity, the cardiovascular protective effect of kaempferol may be mediated, at least in part, by the suppression of VSMC proliferation, which is due to the inhibition of PDGF-R beta tyrosine phosphorylation and its downstream intracellular signal transduction.