title: Adrenal androgen dehydroepiandrosterone sulfate inhibits vascular remodeling following arterial injury.
abstract: Recent epidemiologic studies have suggested that serum dehydroepiandrosterone sulfate (DHEAS) levels have a significant inverse correlation with the incidence of cardiovascular diseases. However, direct evidence for the association with DHEAS and vascular disorders has not yet been explored. DHEAS significantly reduced neointima formation 28 days after surgery without altering other serum metabolite levels in a rabbit carotid balloon injury model. Immunohistochemical analyses revealed the reduction of proliferating cell nuclear antigen (PCNA) index and increase of TdT-mediated dUTP-biotin Nick End Labeling (TUNEL) index, expressing differentiated vascular smooth muscle cell (VSMC) markers in the media 7 days after surgery. In vitro, DHEAS exhibited inhibitory effects on VSMC proliferation and migration activities, inducing G1 cell cycle arrest with upregulation of one of the cyclin dependent kinase (CDK) inhibitors p16(INK4a) and apoptosis with activating peroxisome proliferator-activated receptor (PPAR)-alpha in VSMCs. DHEAS inhibits vascular remodeling reducing neointima formation after vascular injury via its effects on VSMC phenotypic modulation, functions and apoptosis upregulating p16(INK4a)/activating PPARalpha. DHEAS may play a pathophysiological role for vascular remodeling in cardiovascular disease.
authors.affiliation: The First Department of Internal Medicine, Osaka Medical College, Osaka, Japan. masa0331@mac.com
authors.forename: Masaaki
authors.initials: M
authors.lastname: Ii
authors.forename: Masaaki
authors.initials: M
authors.lastname: Hoshiga
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Negoro
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Fukui
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nakakoji
authors.forename: Eiko
authors.initials: E
authors.lastname: Kohbayashi
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Shibata
authors.forename: Daisuke
authors.initials: D
authors.lastname: Furutama
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ishihara
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Hanafusa
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Losordo
authors.forename: Nakaaki
authors.initials: N
authors.lastname: Ohsawa
mesh_terms: D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D020212:Carotid Artery Injuries / Q000503:physiopathology*; D002453:Cell Cycle / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D019314:Dehydroepiandrosterone Sulfate / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000503:physiopathology; D011817:Rabbits; D017539:Tunica Intima / Q000187:drug effects; D015854:Up-Regulation
chemical_list: D000728:Androgens; D019941:Cyclin-Dependent Kinase Inhibitor p16; D019314:Dehydroepiandrosterone Sulfate