Meso-dihydroguaiaretic acid inhibits rat aortic vascular smooth muscle cell proliferation by suppressing phosphorylation of platelet-derived growth factor receptor beta.

Abnormal proliferation of vascular smooth muscle cells (VSMCs) plays an essential functional role in the pathogenesis of vascular disorders, such as atherosclerosis, restenosis, and neointimal hyperplasia. In this study, we examined the effects of meso-dihydroguaiaretic acid (MDGA) on platelet-derived growth factor (PDGF)-BB-induced proliferation and the molecular basis of its underlying mechanism of action in rat aortic VSMCs. Incubation of resting VSMCs with MDGA for 24 h significantly diminished PDGF-BB-induced DNA synthesis in a dose-dependent manner. We also examined the effects of MDGA on PDGF-BB signal transduction. Pre-treatment of VSMCs with MDGA inhibited PDGF-BB-induced phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2), p38, and C-Jun N-terminal kinase (JNK). MDGA also effectively inhibited phosphorylation of Akt, phospholipase C gamma 1 (PLCγ1), and PDGF receptor beta (PDGFRβ). These results indicate that MDGA may inhibit proliferation of VSMCs by suppressing autophosphorylation of PDGFRβ, and may be useful in the treatment of VSMC-associated vascular disease such as atherosclerosis, restenosis, and neointimal hyperplasia after angioplasty.