EGb761 ameliorates the formation of foam cells by regulating the expression of SR-A and ABCA1: Role of haem oxygenase-1

Jin Yi Tsai, Kuo Hui Su, Song Kun Shyue, Yu Ru Kou, Yuan Bin Yu, Sheng Huang Hsiao, An Na Chiang, Yuh Lin Wu, Li Chieh Ching, Tzong Shyuan Lee*

*此作品的通信作者

研究成果: Article同行評審

70 引文 斯高帕斯(Scopus)

摘要

AimsAccumulation of foam cells in the intima is a hallmark of early-stage atherosclerotic lesions. Ginkgo biloba extract (EGb761) has been reported to exert anti-oxidative and anti-inflammatory properties in atherosclerosis, yet the significance and the molecular mechanisms of action of EGb761 in the formation of macrophage foam cells are not fully understood.Methods and resultsTreatment with EGb761 resulted in a dose-dependent decrease in oxidized low-density lipoprotein (oxLDL)-mediated cholesterol accumulation in macrophages, a consequence that was due to a decrease in cholesterol uptake and an increase in cholesterol efflux. Additionally, EGb761 significantly down-regulated the mRNA and protein expression of class A scavenger receptor (SR-A) by decreasing expression of activator protein 1 (AP-1); however, EGb761 increased the protein stability of ATP-binding cassette transporter A1 (ABCA1) by reducing calpain activity without affecting ABCA1 mRNA expression. Small interfering RNA (siRNA) targeting haem oxygenase-1 (HO-1) abolished the EGb761-induced protective effects on the expression of AP-1, SR-A, ABCA1, and calpain activity. Accordingly, EGb761-mediated suppression of lipid accumulation in foam cells was also abrogated by HO-1 siRNA. Moreover, the lesion size of atherosclerosis was smaller in EGb761-treated, apolipoprotein E-deficient mice compared with the vehicle-treated mice, and the expression of HO-1, SR-A, and ABCA1 in aortas was modulated similar to that observed in macrophages. ConclusionThese findings suggest that EGb761 confers a protection from the formation of foam cells by a novel HO-1-dependent regulation of cholesterol homeostasis in macrophages.

原文English
頁(從 - 到)415-423
頁數9
期刊Cardiovascular Research
88
發行號3
DOIs
出版狀態Published - 1 12月 2010

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