肾上腺雄激素硫酸脱氢表雄酮可抑制动脉损伤后的血管重塑。
Adrenal androgen dehydroepiandrosterone sulfate inhibits vascular remodeling following arterial injury.
作者信息
Ii Masaaki, Hoshiga Masaaki, Negoro Nobuyuki, Fukui Ryosuke, Nakakoji Takahiro, Kohbayashi Eiko, Shibata Nobuhiko, Furutama Daisuke, Ishihara Tadashi, Hanafusa Toshiaki, Losordo Douglas W, Ohsawa Nakaaki
机构信息
The First Department of Internal Medicine, Osaka Medical College, Osaka, Japan.
出版信息
Atherosclerosis. 2009 Sep;206(1):77-85. doi: 10.1016/j.atherosclerosis.2009.02.021. Epub 2009 Feb 27.
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.
近期的流行病学研究表明，血清硫酸脱氢表雄酮（DHEAS）水平与心血管疾病的发病率呈显著负相关。然而，DHEAS与血管疾病之间关联的直接证据尚未得到探究。在兔颈动脉球囊损伤模型中，DHEAS在术后28天显著减少了新生内膜的形成，且未改变其他血清代谢物水平。免疫组织化学分析显示，术后7天，增殖细胞核抗原（PCNA）指数降低，而TdT介导的dUTP生物素缺口末端标记（TUNEL）指数升高，同时在中膜表达分化型血管平滑肌细胞（VSMC）标志物。在体外，DHEAS对VSMC的增殖和迁移活动具有抑制作用，通过上调细胞周期蛋白依赖性激酶（CDK）抑制剂之一p16（INK4a）诱导G1期细胞周期阻滞，并通过激活VSMC中的过氧化物酶体增殖物激活受体（PPAR）-α诱导细胞凋亡。DHEAS通过对VSMC表型调节、功能及上调p16（INK4a）/激活PPARα诱导凋亡的作用，抑制血管重塑，减少血管损伤后的新生内膜形成。DHEAS可能在心血管疾病的血管重塑中发挥病理生理作用。
Zotero 插件