Dehydroepiandrosterone anti-atherogenesis effect is not via its conversion to estrogen

• 来源期刊: 中国药理学报（英文版）
• 关键词: dehydroepiandrosterone cytochrome P450 aromatase all-trans retinoic acid atherosclerosis transfection MCP-1 VCAM-1
• 年，卷（期）: 2009,（1）
• 页码范围: 42-53
• 页数: 12页
• 语种: 英文
• DOI: 10.1038/aps.2008.14

摘要

Aim: This study was conducted to demonstrate the anti-atherosclerotic effect of dehydroepiandrosterone (DHEA) and to investigate its possible mechanisms and whether this effect is related to its conversion to estrogen. Methods: Forty male New Zealand White rabbits aged 3 months were divided into 5 groups (n=8 per group) and fed dif-ferent diets for 10 weeks. Serum lipid levels, the area of atherosclerotic lesions and the mRNA levels of monocyte chemoat-tractant protein-1 (MCP-1) and vascular cell adhesion molecule-1 (VCAM-1) in aortic lesions were measured. Then cultured vascular smooth muscle cells (VSMCs) stimulated by oxidized low density lipoprotein-cholesterol (ox-LDL) were treated by DHEA. The gene and protein expression levels of MCP-1 and VCAM-1 in VSMCs was detected. The plasmid with or with-out the gene of cytochrome P450 aromatase (CYP19) was transient transfected into cultured VSMCs respectively. Twenty hours later, the cells were stimulated with ox-LDL and DHEA. Results: DHEA could obviously decrease the area of atherosclerotic lesions and the expressions of MCP-1 and VCAM-1 in aortic lesions. But all-trans retinoic acid (atRA) which was reported would limit restenosis after balloon angioplasty had no visible synergistic effect with DHEA. DHEA could also reduce ox-LDL-induced MCP-1 and VCAM-1 expression in un-transfected or transfected VSMCs. Conclusion: The anti-atherosclerotic effect of DHEA had nothing to do with the catalysis of cytochrome P450 aromatase (CYP19), or was not related to its conversion to estrogen.