Many population studies have shown that blood concentrations of high‐density lipoprotein (HDL) cholesterol are inversely correlated with risk of cardiovascular disease (CVD). However, in recent studies, increasing blood HDL cholesterol concentrations failed to reduce CVD events. On the other hand, studies suggest that improving HDL quality can be a more efficient tool for assessing atherosclerotic risk than simply measuring blood HDL cholesterol concentration. Thus, improving HDL activity using natural substances might be a useful therapeutic approach to reducing CVD risk. We previously isolated a novel active compound from Nannochloropsis microalgae termed lyso‐diacylglyceryltrimethylhomoserine (lyso‐DGTS), which increased activity of paraoxonase 1, the main antioxidant enzyme associated with HDL. Here we examined the effect of lyso‐DGTS on HDL quality and function. Tryptophan‐fluorescence‐quenching assay showed that lyso‐DGTS interacts spontaneously with the entire HDL lipoprotein and with apolipoprotein A1 (ApoA1), the major structural and functional HDL protein, with high affinity (K_a = 2.17 × 10⁴ M⁻¹ at 37°C). Lyso‐DGTS added to HDL and to ApoA1 increased cholesterol efflux from macrophage cells, the main antiatherogenic function of HDL, dose‐dependently, and significantly increased HDL's ability to induce nitric oxide production from endothelial cells. In‐vivo supplementation of lyso‐DGTS to the circulation of mice fed a high‐fat diet via osmotic mini‐pumps implanted subcutaneously enhanced HDL anti‐inflammatory effect significantly as compared to controls. Our findings suggest that lyso‐DGTS may have a beneficial effect in decreasing atherosclerosis risk by interacting with HDL particles and improving their quality and antiatherogenic functions.

中文翻译：

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从Nannochloropsis微藻中分离出的溶血二酰基甘油基三甲基高丝氨酸（lyso-DGTS）改善了高密度脂蛋白（HDL）的功能。

许多人口研究表明，血液中高密度脂蛋白（HDL）胆固醇的浓度与心血管疾病（CVD）的风险呈负相关。但是，在最近的研究中，增加血液中HDL胆固醇的浓度未能减少CVD事件。另一方面，研究表明，与简单地测量血液中HDL胆固醇浓度相比，提高HDL质量可以是评估动脉粥样硬化风险的更有效工具。因此，使用天然物质改善HDL活性可能是降低CVD风险的有用治疗方法。我们先前从Nannochloropsis分离了一种新型活性化合物微藻称为溶血二酰基甘油三甲基高丝氨酸（lyso-DGTS），可增加对氧磷合酶1（与HDL相关的主要抗氧化酶）的活性。在这里，我们检查了溶血酶DGTS对HDL质量和功能的影响。色氨酸荧光猝灭测定表明，溶血酶DGTS与整个HDL脂蛋白以及载脂蛋白A1（ApoA1）自发相互作用，载脂蛋白A1是主要的结构和功能性HDL蛋白，具有高亲和力（K _a = 2.17×10 ⁴  M ^-1在37°C下）。添加到HDL和ApoA1中的Lyso-DGTS剂量依赖性地增加了巨噬细胞胆固醇的流出，这是HDL的主要抗动脉粥样硬化功能，并且显着提高了HDL诱导内皮细胞产生一氧化氮的能力。与皮下注射相比，通过皮下植入的渗透性微型泵对高脂饮食喂养的小鼠体内进行溶血DGTS的体内补充显着增强了HDL的抗炎作用。我们的研究结果表明，溶血DGTS通过与HDL颗粒相互作用并改善其质量和抗动脉粥样硬化功能，可能在降低动脉粥样硬化风险方面具有有益作用。