title: Hispolon attenuates balloon-injured neointimal formation and modulates vascular smooth muscle cell migration via AKT and ERK phosphorylation.
abstract: The pathological mechanism of restenosis is attributed primarily to excessive proliferation and migration of vascular smooth muscle cells (VSMC). The preventive effects of hispolon (1) on balloon injury-induced neointimal formation were investigated, and 1 showed potent activity in inhibiting fetal bovine serum-induced VSMC outgrowth. Hispolon (1) significantly inhibited VSMC migration, as shown by trans-well assays. Compound 1 decreased the expression and secretion of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). The expression of the endogenous inhibitors of these proteins, namely, tissue inhibitors of MMP (TIMP-1 and TIMP-2), increased. The inhibition by noncytotoxic doses of 1 of VSMC migration was through its negative regulatory effects on FAK phosphorylation, ERK1/2 phosphorylation, and PI3K/AKT. These results demonstrate that 1 can inhibit the migration of VSMC by reduced expression of MMP-9 through the suppression of the FAK signaling pathway and of the activity of PI3K/AKT. The data obtained suggest that 1 might block balloon injury-induced neointimal hyperplasia via the inhibition of VSMC proliferation and migration, without inducing apoptosis.
authors.affiliation: Department of Life Science and Agricultural Biotechnology Center, National Chung Hsing University, Taichung 402, Taiwan.
authors.forename: Yi-Chung
authors.initials: YC
authors.lastname: Chien
authors.forename: Guang-Jhong
authors.initials: GJ
authors.lastname: Huang
authors.forename: Hsu-Chen
authors.initials: HC
authors.lastname: Cheng
authors.forename: Chieh-Hsi
authors.initials: CH
authors.lastname: Wu
authors.forename: Ming-Jyh
authors.initials: MJ
authors.lastname: Sheu
mesh_terms: D000818:Animals; D002396:Catechols / Q000737:chemistry / Q000494:pharmacology*; D002417:Cattle; D006965:Hyperplasia / Q000139:chemically induced; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D015394:Molecular Structure; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
chemical_list: D002396:Catechols; C103442:hispolon; D051057:Proto-Oncogene Proteins c-akt; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9