Winthrop Research Institute, Department of Medicine, Winthrop University Hospital, 222 Station Plaza, North, Suite 511B, Mineola, NY 11501, USA.
Eur J Pharmacol. 2013 Jan 5;698(1-3):299-309. doi: 10.1016/j.ejphar.2012.08.024. Epub 2012 Oct 4.
Resveratrol is a bioactive molecule used in dietary supplements and herbal medicines and consumed worldwide. Known cardioprotective and anti-inflammatory properties of resveratrol have spurred investigation of the mechanisms involved. The present study explored potential atheroprotective actions of resveratrol on cholesterol metabolism in cells of the arterial wall, including human macrophages and arterial endothelium. Using QRT-PCR and Western blotting techniques, we measured expression of the proteins involved in reverse cholesterol transport (ABCA1, ABCG1 and SR-B1) and the scavenger receptors responsible for uptake of modified cholesterol (CD36, SR-A1 and LOX-1). We analyzed the effect of resveratrol on apoA-1-and HDL-mediated cholesterol efflux in human THP-1 macrophages. The effect of resveratrol on oxLDL internalization and foam cell formation were evaluated using confocal and light microscopy. Our data indicate that resveratrol regulates expression of major proteins involved in cholesterol transport, promotes apoA-1 and HDL-mediated efflux, downregulates oxLDL uptake and diminishes foam cell formation. Mechanistically, resveratrol effects were dependent upon PPAR-γ and adenosine 2A receptor pathways. For the first time we demonstrate that resveratrol regulates expression of the cholesterol metabolizing enzyme cytochrome P450 27-hydroxylase, providing efficient cholesterol elimination via formation of oxysterols. This study establishes that resveratrol attenuates lipid accumulation in cultured human macrophages via effects on cholesterol transport. Further in vivo studies are needed to determine whether resveratrol may be an additional resource available to reduce lipid deposition and atherosclerosis in humans.
白藜芦醇是一种生物活性分子，用于膳食补充剂和草药，并在全球范围内消费。白藜芦醇具有已知的心脏保护和抗炎特性，这激发了对相关机制的研究。本研究探讨了白藜芦醇对动脉壁细胞（包括人巨噬细胞和动脉内皮细胞）胆固醇代谢的潜在动脉保护作用。使用 QRT-PCR 和 Western blot 技术，我们测量了涉及胆固醇逆转运的蛋白质（ABCA1、ABCG1 和 SR-B1）和负责摄取修饰胆固醇的清道夫受体（CD36、SR-A1 和 LOX-1）的表达。我们分析了白藜芦醇对人 THP-1 巨噬细胞中载脂蛋白 A-1 和高密度脂蛋白介导的胆固醇流出的影响。使用共聚焦和光学显微镜评估了白藜芦醇对氧化低密度脂蛋白（oxLDL）内化和泡沫细胞形成的影响。我们的数据表明，白藜芦醇调节参与胆固醇转运的主要蛋白质的表达，促进载脂蛋白 A-1 和高密度脂蛋白介导的流出，下调 oxLDL 摄取并减少泡沫细胞形成。在机制上，白藜芦醇的作用取决于 PPAR-γ 和腺苷 2A 受体途径。我们首次证明，白藜芦醇调节胆固醇代谢酶细胞色素 P450 27-羟化酶的表达，通过形成氧化固醇提供有效的胆固醇消除。这项研究表明，白藜芦醇通过影响胆固醇转运来减轻培养的人巨噬细胞中的脂质积累。需要进一步的体内研究来确定白藜芦醇是否可能是减少人类脂质沉积和动脉粥样硬化的另一种可用资源。
