VA Palo Alto Health Care System, Palo Alto, CA, United States; Stanford University, Department of Cardiovascular Medicine, Stanford, CA, United States; Department of Vascular and Endovascular Surgery, University Hospital Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany.
VA Palo Alto Health Care System, Palo Alto, CA, United States; Stanford University, Department of Cardiovascular Medicine, Stanford, CA, United States.
Atherosclerosis. 2020 Oct;311:73-83. doi: 10.1016/j.atherosclerosis.2020.08.012. Epub 2020 Aug 29.
Hyperlipidemia is a suggested risk factor for abdominal aortic aneurysm (AAA). However, whether hyperlipidemia is causally involved in AAA progression remains elusive. Here, we tested the hypothesis that hyperlipidemia aggravates AAA formation in the widely used porcine pancreatic elastase (PPE) model of AAA in mice with varying levels of plasma lipids.
Prior to PPE-surgery, 8-week-old male C57BL/6J mice (n = 32) received 1·10 viral genomes of rAAV8-D377Y-mPcsk9 or control rAAV8 via the tail vein. Mice were fed either western type diet or regular chow. At baseline and during the 28 days following PPE-surgery, mice underwent weekly ultrasonic assessment of AAA progression. Experiments were repeated using Apolipoprotein E knockout (ApoE) mice (n = 7) and wildtype C57BL/6J mice (n = 5).
At sacrifice, maximal intergroup plasma cholesterol and non-HDL/HDL ratio differences were >5-fold and >20-fold, respectively. AAA diameters expanded to 150% of baseline, but no intergroup differences were detected. This was verified in an independent experiment comparing 8-week-old male ApoE mice with wildtype mice. Histological evaluation of experimental AAA lesions revealed accumulated lipid in neointimal and medial layers, and analysis of human AAA lesions (n = 5) obtained from open repair showed medial lipid deposition.
In summary, we find that lipid deposition in the aortic wall is a feature of PPE-induced AAA in mice as well as human AAA lesions. Despite, our data do not support the hypothesis that hyperlipidemia contributes to AAA progression.
高血脂被认为是腹主动脉瘤（AAA）的一个风险因素。然而，高血脂是否与 AAA 的进展有关仍不清楚。在这里，我们通过在不同血脂水平的小鼠中广泛应用的猪胰弹性蛋白酶（PPE）AAA 模型来检验高血脂是否会加重 AAA 形成的假设。
在 PPE 手术前，8 周龄雄性 C57BL/6J 小鼠（n=32）通过尾静脉接受 1·10 病毒基因组的 rAAV8-D377Y-mPcsk9 或对照 rAAV8。小鼠分别给予西方饮食或普通饲料。在基线和 PPE 手术后的 28 天内，每周对 AAA 进展进行超声评估。使用载脂蛋白 E 敲除（ApoE）小鼠（n=7）和野生型 C57BL/6J 小鼠（n=5）重复实验。
在处死时，最大的组间血浆胆固醇和非 HDL/HDL 比值差异超过 5 倍和 20 倍。AAA 直径扩大到基线的 150%，但未检测到组间差异。这在一项比较 8 周龄雄性 ApoE 小鼠和野生型小鼠的独立实验中得到了验证。对实验性 AAA 病变的组织学评估显示，在内膜和中层有脂质堆积，对取自开放修复的人类 AAA 病变（n=5）的分析显示中层有脂质沉积。
总之，我们发现主动脉壁中的脂质沉积是 PPE 诱导的小鼠 AAA 以及人类 AAA 病变的一个特征。尽管我们的数据不支持高血脂促进 AAA 进展的假设。
