Phytoestrogen derivatives differentially inhibit arterial neointimal proliferation in a mouse model

作者：Shen, Jie; White, Melanie; Hu**and, Alan J; Hambly, Brett D; Bao, Shisan^*

来源：European Journal of Pharmacology, 2006, 548(1-3): 123-128.

DOI：10.1016/j.ejphar.2006.07.050

• phytoestrogen
• dihydrodaidzein
• atherosclerosis
• restenosis after angioplasty
• vascular smooth muscle cell proliferation

Neointimal proliferation is a key element in atherosclerotic plaque formation and in arterial restenosis following angioplasty. Estrogen-like compounds, including naturally occurring plant phytoestrogens, are known to alter the extent of neointimal proliferation. This study investigates the anti-atherogenic/restenotic effect of several synthetic metabolites of isoflavone phytoestrogens (dihydrodaidzein, tetrahydrodaidzein and dehydroequol) (Novogen, Sydney, Australia). Acute neointimal proliferation was induced in the iliac artery of cholesterol-fed mice, by mechanically damaging the endothelium. Phytoestrogens were administered orally for 4 weeks and the damaged arteries harvested. Intimal area, as a percentage of the iliac artery wall area, was measured. Dihydrodaidzein significantly halved the intimal response (intima similar to 25% of wall area; p < 0.01) compared with placebo diet-fed mice (intima similar to 50% of wall area), while tetrahydrodaidzein and dehydroequol showed no inhibitory effects. Immunohistochemistry demonstrated that alpha-actin-positive vascular smooth muscle cells were the major cell type in the proliferating neointima. A single layer of endothelium covered the thickened intima by 4 weeks. Thus, a specific phytoestrogen isoflavone compound (dihydrodaidzein) can selectively inhibit neointimal proliferation, either by inhibition of vascular smooth muscle cell migration and proliferation, and/or by enhancing endothelial proliferation and function, and inhibition of endothelial apoptosis.

• 出版日期2006-10-24
• 单位上海交通大学