| Literature DB >> 19298964 |
Masaaki Ii1, Masaaki Hoshiga, Nobuyuki Negoro, Ryosuke Fukui, Takahiro Nakakoji, Eiko Kohbayashi, Nobuhiko Shibata, Daisuke Furutama, Tadashi Ishihara, Toshiaki Hanafusa, Douglas W Losordo, Nakaaki Ohsawa.
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.Entities:
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Year: 2009 PMID： 19298964 PMCID： PMC2735614 DOI： 10.1016/j.atherosclerosis.2009.02.021
Source DB: PubMed Journal: Atherosclerosis ISSN： 0021-9150 Impact factor: 5.162