Adrenal androgen dehydroepiandrosterone sulfate inhibits vascular remodeling following arterial injury

被引：24

作者：

Ii, Masaaki ^{[1
,2
]}

Hoshiga, Masaaki ^{[2
]}

Negoro, Nobuyuki ^{[2
]}

Fukui, Ryosuke ^{[2
]}

Nakakoji, Takahiro ^{[2
]}

Kohbayashi, Eiko ^{[2
]}

Shibata, Nobuhiko ^{[2
]}

Furutama, Daisuke ^{[2
]}

Ishihara, Tadashi ^{[2
]}

Hanafusa, Toshiaki ^{[2
]}

Losordo, Douglas W. ^{[3
]}

Ohsawa, Nakaaki ^{[4
]}

机构：

[1] Inst Biomed Res & Innovat, Grp Vasc Regenerat Res, Chuo Ku, Kobe, Hyogo 6500047, Japan

[2] Osaka Med Coll, Dept Internal Med 1, Osaka, Japan

[3] Northwestern Univ, Feinberg Sch Med, Feinberg Cardiovasc Res Inst, Chicago, IL 60611 USA

[4] Aino Inst Aging Res, Osaka, Japan

来源：

ATHEROSCLEROSIS | 2009年 / 206卷 / 01期

关键词：

Hormones; Restenosis; Vascular smooth muscle cell; Apoptosis; SMOOTH-MUSCLE-CELLS; MYOCARDIAL-INFARCTION; CDNA CLONING; PPAR-ALPHA; ATHEROSCLEROSIS; RABBIT; RESTENOSIS; FIBROBLASTS; MIGRATION; KINASE;

D O I：

10.1016/j.atherosclerosis.2009.02.021

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 PPAR alpha. DHEAS may play a pathophysiological role for vascular remodeling in cardiovascular disease. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

引用

页码：77 / 85

页数：9

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