Cardiovascular Program ICCC, Institut de Recerca, Hospital Santa Creu i Sant Pau, IIB Sant Pau, 08025 Barcelona, Spain.
Faculty of Medicine, University of Barcelona (UB), 08036 Barcelona, Spain.
Int J Mol Sci. 2022 Aug 2;23(15):8596. doi: 10.3390/ijms23158596.
High-density lipoproteins (HDL) undergo adverse remodeling and loss of function in the presence of comorbidities. We assessed the potential of lipid-lowering approaches (diet and rosuvastatin) to rescue hypercholesterolemia-induced HDL dysfunction. Hypercholesterolemia was induced in 32 pigs for 10 days. Then, they randomly received one of the 30-day interventions: (I) hypercholesterolemic (HC) diet; (II) HC diet + rosuvastatin; (III) normocholesterolemic (NC) diet; (IV) NC diet + rosuvastatin. We determined cholesterol efflux capacity (CEC), antioxidant potential, HDL particle number, HDL apolipoprotein content, LDL oxidation, and lipid levels. Hypercholesterolemia time-dependently impaired HDL function (−62% CEC, −11% antioxidant index (AOI); p < 0.01), increased HDL particles numbers 2.8-fold (p < 0.0001), reduced HDL-bound APOM (−23%; p < 0.0001), and increased LDL oxidation 1.7-fold (p < 0.0001). These parameters remained unchanged in animals on HC diet alone up to day 40, while AOI deteriorated up to day 25 (−30%). The switch to NC diet reversed HDL dysfunction, restored apolipoprotein M content and particle numbers, and normalized cholesterol levels at day 40. Rosuvastatin improved HDL, AOI, and apolipoprotein M content. Apolipoprotein A-I and apolipoprotein C-III remained unchanged. Lowering LDL-C levels with a low-fat diet rescues HDL CEC and antioxidant potential, while the addition of rosuvastatin enhances HDL antioxidant capacity in a pig model of hypercholesterolemia. Both strategies restore HDL-bound apolipoprotein M content.
高密度脂蛋白（HDL）在合并症存在的情况下会发生不利的重构和功能丧失。我们评估了降脂方法（饮食和瑞舒伐他汀）恢复高胆固醇血症诱导的 HDL 功能障碍的潜力。在 32 头猪中诱导高胆固醇血症 10 天。然后，它们随机接受以下 30 天干预措施之一：（I）高胆固醇血症（HC）饮食；（II）HC 饮食+瑞舒伐他汀；（III）正常胆固醇血症（NC）饮食；（IV）NC 饮食+瑞舒伐他汀。我们测定了胆固醇流出能力（CEC）、抗氧化潜力、HDL 颗粒数、HDL 载脂蛋白含量、LDL 氧化和脂质水平。高胆固醇血症使 HDL 功能呈时间依赖性受损（CEC 降低 62%，抗氧化指数（AOI）降低 11%；p < 0.01），HDL 颗粒数增加 2.8 倍（p < 0.0001），HDL 结合的 APOM 减少 23%（p < 0.0001），LDL 氧化增加 1.7 倍（p < 0.0001）。在单独给予 HC 饮食的动物中，这些参数在第 40 天之前保持不变，而 AOI 在第 25 天恶化（降低 30%）。转换为 NC 饮食可逆转 HDL 功能障碍，恢复载脂蛋白 M 含量和颗粒数，并使胆固醇水平在第 40 天恢复正常。瑞舒伐他汀可改善 HDL、AOI 和载脂蛋白 M 含量。载脂蛋白 A-I 和载脂蛋白 C-III 保持不变。低脂饮食降低 LDL-C 水平可挽救 HDL 的 CEC 和抗氧化潜力，而瑞舒伐他汀可增强高胆固醇血症猪模型中 HDL 的抗氧化能力。两种策略都可恢复 HDL 结合的载脂蛋白 M 含量。
