Mansouri Roxane M, Baugé Eric, Gervois Philippe, Fruchart-Najib Jamila, Fiévet Catherine, Staels Bart, Fruchart Jean-Charles
Inserm, U545, Institut Pasteur de Lille, Lille F-59019, France.
Circ Res. 2008 Aug 29;103(5):450-3. doi: 10.1161/CIRCRESAHA.108.179861. Epub 2008 Jul 24.
Hypertriglyceridemia is an independent risk factor for coronary artery disease. Because apolipoprotein (Apo)A5 regulates plasma triglyceride levels, we investigated the impact of human (h)ApoA5 on atherogenesis. The influence of hApoA5 transgenic expression was studied in the ApoE2 knock-in mouse model of mixed dyslipidemia. Our results demonstrate that hApoA5 lowers plasma triglyceride levels in Western diet-fed ApoE2 knock-in mice. Moreover, atherosclerotic lesion development was significantly decreased in the hApoA5 transgenic mice. Finally, pharmacologic activation of hApoA5 expression by the peroxisome proliferator-activated receptor-alpha agonist fenofibrate resulted in an enhanced atheroprotection. These results identify an atheroprotective role of hApoA5 in a mouse model of mixed dyslipidemia.
高甘油三酯血症是冠状动脉疾病的独立危险因素。由于载脂蛋白（Apo）A5调节血浆甘油三酯水平，我们研究了人（h）ApoA5对动脉粥样硬化形成的影响。在混合性血脂异常的ApoE2基因敲入小鼠模型中研究了hApoA5转基因表达的影响。我们的结果表明，hApoA5可降低西方饮食喂养的ApoE2基因敲入小鼠的血浆甘油三酯水平。此外，hApoA5转基因小鼠的动脉粥样硬化病变发展显著减少。最后，过氧化物酶体增殖物激活受体-α激动剂非诺贝特对hApoA5表达的药物激活导致动脉粥样硬化保护作用增强。这些结果确定了hApoA5在混合性血脂异常小鼠模型中的动脉粥样硬化保护作用。
