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VLDL和LDL胆固醇水平升高与动脉粥样硬化风险相关；因此，目前的药物脂质调节主要集中在降低LDL-C和TG水平上。然而，这一策略仅将心血管发病率和死亡率降低了25%。因此，提高HDL-C水平最近成为一种有希望的CVD治疗靶点。在本研究中，通过灌胃给予聚乙二醇化和季铵化多胺纳米凝胶，以研究该治疗如何调节血清VLDL/LDL-C水平。有趣的是，我们发现纳米凝胶不仅降低了小鼠的VLDL/LDL-C水平，而且显著提高了HDL-C水平并减少了动脉粥样硬化病变。口服纳米凝胶可能是未来通过提高HDL-C水平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.