Liang Bin, Wang Xin, Guo Xiaohong, Yang Zhiming, Bai Rui, Liu Ming, Xiao Chuanshi, Bian Yunfei
Department of Cardiology, Second Hospital of Shanxi Medical University 382 Wuyi Road, Taiyuan, China.
Department of Rheumatology, Second Hospital of Shanxi Medical University 382 Wuyi Road, Taiyuan, China.
Int J Clin Exp Pathol. 2015 Jan 1;8(1):450-7. eCollection 2015.
ATP-binding cassette transporter A1 (ABCA1) plays a crucial role in reverse cholesterol transport and anti-atherosclerosis. Liver X receptor alpha (LXRα) can stimulate cholesterol efflux through ABCA1. It has been well known that adiponectin has cardiovascular protection. In this study, we attempted to clarify the effect of adiponectin on expression of ABCA1, and explored the role of LXRα in the regulation of ABCA1 in RAW 264.7 macrophages. Our results showed that adiponectin increased ABCA1 expression at both the mRNA and protein levels in a dose-dependent and time-dependent manner. Consequently, adiponectin promoted cholesterol efflux and decreased cholesterol content in RAW 264.7 macrophages. Moreover, adiponectin up-regulated the expression of LXRα in a dose-dependent and time-dependent manner in RAW 264.7 macrophages. LXRα small interfering RNA completely abolished the promotion effects of adiponectin. In summary, adiponectin up-regulates ABCA1 expression via the LXRα pathway in RAW 264.7 macrophages. This novel insight could prove useful for developing new treatment strategies for cardiovascular diseases.
ATP结合盒转运蛋白A1(ABCA1)在胆固醇逆向转运和抗动脉粥样硬化过程中发挥着关键作用。肝脏X受体α(LXRα)可通过ABCA1刺激胆固醇外流。众所周知,脂联素具有心血管保护作用。在本研究中,我们试图阐明脂联素对ABCA1表达的影响,并探讨LXRα在RAW 264.7巨噬细胞中对ABCA1调控的作用。我们的结果表明,脂联素在mRNA和蛋白质水平上均以剂量和时间依赖性方式增加ABCA1的表达。因此,脂联素促进RAW 264.7巨噬细胞中的胆固醇外流并降低胆固醇含量。此外,脂联素在RAW 264.7巨噬细胞中以剂量和时间依赖性方式上调LXRα的表达。LXRα小干扰RNA完全消除了脂联素的促进作用。总之,脂联素通过RAW 264.7巨噬细胞中的LXRα途径上调ABCA1表达。这一新见解可能对开发心血管疾病的新治疗策略有用。