Garlic extract methylallyl thiosulfinate blocks insulin potentiation of platelet-derived growth factor-stimulated migration of vascular smooth muscle cells.

Platelet-derived growth factor (PDGF) is a potent inducer of vascular smooth muscle cell (VSMC) migration, whereas insulin, in physiological concentrations, helps maintain the nonproliferative phenotype of these cells. However, hyperinsulinemia (10 nmol/L) significantly potentiates the PDGF (30 pmol/L)-induced migration of VSMC. This potentiating effect of hyperinsulinemia appears to be mediated by increased availability of geranylgeranylated Rho-A. Hyperinsulinemia significantly increased the activity of geranylgeranyltransferase I (GGTase I) and the amounts of prenylated Rho-A. This action of hyperinsulinemia was inhibited by methylallyl thiosulfinate (MAT), a component of garlic extract, which exerted a strong anti-GGTase I activity. MAT also completely inhibited the ability of hyperinsulinemia to potentiate the PDGF-induced VSMC migration. Thus, the purported anti-atherogenic action of garlic may be related to its inhibitory influence on GGTase I.