Evaluation and exploratory mechanistic analysis; how a novel nano technology increases serum HDL levels by oral administration in mice.

心血管疾病(CVD)是现代社会最常见的死亡原因。血清极低密度脂蛋白和低密度脂蛋白水平升高与动脉粥样硬化的风险相关；因此，目前的药物调脂主要集中在降低低密度脂蛋白和甘油三酯水平上。然而，这一策略仅将心血管发病率和死亡率降低了高达25%。因此，提高高密度脂蛋白-C水平是最近出现的一个有希望的治疗心血管疾病的靶点。在本研究中，通过灌胃给予聚乙二醇化和季节化多胺纳米凝胶来研究治疗如何调节血清VLDL/LDL-C水平。有趣的是，我们发现纳米凝胶不仅降低了极低密度脂蛋白/低密度脂蛋白-C的水平，而且显著提高了高密度脂蛋白-C的水平，减少了小鼠的动脉粥样硬化病变。口服纳米凝胶可能是未来通过提高高密度脂蛋白-C水平来治疗动脉粥样硬化的一种新的治疗策略。

Cardiovascular disease (CVD) is the most common cause of mortality in the modern society. Elevated serum VLDL and LDL cholesterol levels are associated with a risk for atherosclerosis; thus, the current pharmaceutical lipid modulation has been mainly focused on lowering LDL-C and TG levels. However, this strategy has reduced cardiovascular morbidity and mortality by only up to 25%. Therefore, raising HDL-C levels has recently emerged as a promising therapeutic target for CVD.In this study, PEGylated and quaternized polyamine nanogel was administered via gavage to examine how the treatment modulates serum VLDL/LDL-C levels. We interestingly found that the nanogel administration not only reduced VLDL/LDL-C levels, but also significantly raised HDL-C levels and reduced atherosclerotic lesions in mice. The oral administration of the nanogel could be a novel therapeutic strategy for treatment of atherosclerosis by raising HDL-C levels in the future.