Centre for Individualized Medicine in Arterial Diseases, Odense University Hospital, Odense, Denmark.
Department of Cardiothoracic and Vascular Surgery, Odense University Hospital, Odense, Denmark.
PLoS One. 2020 Aug 28;15(8):e0234409. doi: 10.1371/journal.pone.0234409. eCollection 2020.
An abdominal aortic aneurysm (AAA) is a progressive chronic dilatation of the abdominal aorta with terminally rupture when the aortic wall is so weakened that aortic wall stress exceeds wall strength. No effective medical treatment exists so far. We aimed to test whether intraluminal admission of Penta-Galloyl Glucose (PGG) treatment in a rodent AAA model could hold the potential to inhibit aneurysmal progression.
Male Sprague Dawley rats had either intraluminal elastase infused for AAA induction or saline to serve as controls. In two independent experimental series, elastase was used to induce AAA followed by an intraluminal PGG (directly or by a drug eluting balloon) treatment. All rats were followed for 28 days and euthanized. In both series, maximal infrarenal aortic diameter was measured at baseline and at termination as a measure of AAA size. In series 2, maximal internally AAA diameter was followed by ultrasound weekly. AAA tissues were analyzed for elastin integrity by millers stain, collagen deposition by masson trichrome staining. In other AAA tissue samples the mRNA level of CD45, lysyloxidase (LOX), lysyloxidase like protein 1 (LOXL1) were determined by qPCR.
Direct administration of PGG significantly reduced AAA expansion when compared to controls. PGG treatment resulted in a higher number and more preserved elastic fibers in the aneurysmal wall, while no significant difference was seen in the levels of CD45 and LOX mRNA levels. The drug eluting balloon (DEB) experiment showed no significant difference in AAA size observed neither macroscopically nor ultrasonically. Also the aneurysmal mRNA levels of CD45, LOX and LOXL1 were unchanged between groups.
A significant reduced expansion of AAAs was observed in the PGG group, suggesting PGG as a drug to inhibit aneurysmal progression, while administration through a DEB did not show a promising new way of administration.
腹主动脉瘤(AAA)是一种进行性的慢性腹主动脉扩张,当主动脉壁变得如此脆弱以至于主动脉壁的应力超过壁的强度时,最终会破裂。到目前为止,还没有有效的医学治疗方法。我们旨在测试在鼠 AAA 模型中腔内给予五倍子酰葡萄糖(PGG)治疗是否有可能抑制动脉瘤的进展。
雄性 Sprague Dawley 大鼠接受腔内弹性蛋白酶输注以诱导 AAA,或接受生理盐水作为对照。在两个独立的实验系列中,用弹性蛋白酶诱导 AAA,然后用腔内 PGG(直接或通过药物洗脱球囊)治疗。所有大鼠均随访 28 天并安乐死。在两个系列中,均在基线和终止时测量肾下最大主动脉直径作为 AAA 大小的指标。在系列 2 中,每周通过超声测量最大内部 AAA 直径。通过米勒染色分析 AAA 组织中的弹性蛋白完整性,通过 Masson 三色染色分析胶原蛋白沉积。在其他 AAA 组织样本中,通过 qPCR 测定 CD45、溶酶体(LOX)、溶酶体样蛋白 1(LOXL1)的 mRNA 水平。
与对照组相比,PGG 的直接给药显著减少了 AAA 的扩张。PGG 治疗导致动脉瘤壁中更多和更保存的弹性纤维,而 CD45 和 LOX mRNA 水平没有显著差异。药物洗脱球囊(DEB)实验显示,在宏观和超声上均未观察到 AAA 大小的显著差异。两组之间 CD45、LOX 和 LOXL1 的动脉瘤 mRNA 水平也没有变化。
PGG 组观察到 AAA 扩张显著减少,表明 PGG 是一种抑制动脉瘤进展的药物,而通过 DEB 给药并没有显示出一种有前途的新给药方式。