Inhibitions of vascular endothelial growth factor expression and foam cell formation by EGb 761, a special extract of Ginkgo biloba, in oxidatively modified low-density lipoprotein-induced human THP-1 monocytes cells

被引:17
作者
Liu, H. J. [2 ]
Wang, X. L. [1 ]
Zhang, L. [3 ]
Qiu, Y. [4 ]
Li, T. J. [1 ]
Li, R. [3 ]
Wu, M. C. [3 ]
Wei, L. X. [3 ]
Rui, Y. C. [1 ]
机构
[1] Second Mil Med Univ, Shanghai 200433, Peoples R China
[2] Secondary Mil Med Univ, Changhai Hosp, Shanghai 200433, Peoples R China
[3] Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Tumor Immunol & Gene Therapy Ctr, Shanghai 200438, Peoples R China
[4] 454th Hosp PLA, Dept Pharm, Nanjing 210002, Peoples R China
基金
中国国家自然科学基金;
关键词
Vascular endothelial growth factor; Ginkgo biloba extract; Atherosclerosis; Oxidized low-density lipoprotein; Foam cells; OXIDIZED LDL; IN-VITRO; GENE-EXPRESSION; INFLAMMATION; ACTIVATION; VEGF; ATHEROSCLEROSIS; DIFFERENTIATION; MACROPHAGES; RECEPTORS;
D O I
10.1016/j.phymed.2008.11.003
中图分类号
Q94 [植物学];
学科分类号
071001 ;
摘要
It has been reported that oxidatively modified low-density lipoprotein (Ox-LDL) involvement with vascular endothelial growth factor (VEGF) and foam cell formation play an important role in atherosclerosis (AS). Protective effects of Ginkgo biloba extract (EGb 761) have been identified for some cardiovascular and neurological disorders. The aim of this study was to investigate whether Ox-LDL regulates VEGF expression in human THP-1 monocytes, as well as the effect of EGb 761 on VEGF expression and the formation of foam cells. After exposure to Ox-LDL alone or in combination with EGb 761 for up to 48 h, cell viability was measured using the MTT assay. VEGF protein content in the supernatant was analyzed by enzyme-linked immunosorbent assay (ELISA). VEGF mRNA was determined by real-time PCR. To determine the effect of EGb 761 on foam cell formation, an Ox-LDL-induced foam cell model was used. Ox-LDL inhibited the growth of THP-1 cells and EGb 761 increased the cell survival rate. Ox-LDL markedly increased VEGF expression in THP-1 cells in a time- and concentration-dependent manner, which was significantly suppressed by EGb 761. EGb 761 also inhibited monocyte/macrophage-derived foam cell formation. These results suggest that Ox-LDL is involved in the development of human AS through VEGF induction in monocytes, and that EGb 761 prevents in vitro atherogenesis, probably via downregulation of VEGF expression in monocytes and inhibition of monocyte/macrophage-derived foam cell formation. The findings suggest a mechanism for the in vivo anti-AS effect of EGb 761 and support its potential clinical use in AS. (C) 2008 Elsevier GmbH. All rights reserved.
引用
收藏
页码:138 / 145
页数:8
相关论文
共 32 条
[11]   RNA interference for HIF-1α inhibits foam cells formation in vitro [J].
Jiang, Guojun ;
Li, Tiejun ;
Qiu, Yan ;
Rui, Yaocheng ;
Chen, Wansheng ;
Lou, Yijia .
EUROPEAN JOURNAL OF PHARMACOLOGY, 2007, 562 (03) :183-190
[12]  
Jiao Ya-bin, 2007, Yaoxue Xuebao, V42, P930
[13]   Expression of pro-inflammatory and anti-inflammatory cytokines in brain of atherosclerotic rats and effects of Ginkgo biloba extract [J].
Jiao, YB ;
Rui, YC ;
Li, TJ ;
Yang, PY ;
Qiu, Y .
ACTA PHARMACOLOGICA SINICA, 2005, 26 (07) :835-839
[14]   Role of angiogenesis in cardiovascular disease - A critical appraisal [J].
Khurana, R ;
Simons, M ;
Martin, JF ;
Zachary, IC .
CIRCULATION, 2005, 112 (12) :1813-1824
[15]   Scavenger receptors class A-I/II and CD36 are the principal receptors responsible for the uptake of modified low density lipoprotein leading to lipid loading in macrophages [J].
Kunjathoor, VV ;
Febbraio, M ;
Podrez, EA ;
Moore, KJ ;
Andersson, L ;
Koehn, S ;
Rhee, JS ;
Silverstein, R ;
Hoff, HF ;
Freeman, MW .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (51) :49982-49988
[16]   Inflammation in Atherosclerosis [J].
Libby, Peter .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2012, 32 (09) :2045-2051
[17]   Ginkgo biloba, inflammation and lipoprotein(a) [J].
Lippi, Giuseppe ;
Targher, Giovanni ;
Guidi, Gian Cesare .
ATHEROSCLEROSIS, 2007, 195 (02) :417-418
[18]  
LIU F, 2007, PHYTOTHER RES
[19]   Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method [J].
Livak, KJ ;
Schmittgen, TD .
METHODS, 2001, 25 (04) :402-408
[20]   Signal transduction via vascular endothelial growth factor (VEGF) receptors and their roles in atherogenesis [J].
Matsumoto, Taro ;
Mugishima, Hideo .
JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS, 2006, 13 (03) :130-135