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Abstract：
Background: Pentagalloyl glucose (PGG) is a polyphenol with vasoprotective properties. Targeted delivery of PGG reversed aortic aneurysm growth in several rodent models associated with decreased number of macrophages and transforming growth factor-β (TGF-β) expression. Thus, we sought to determine cellular mechanisms by which PGG reduces macrophage-induced aortic pathogenicity and its relationship to TGF-β. Methods: Using THP-1 cells, primary human aortic cells, and explanted rat aortas, we assessed the anti-inflammatory effect of PGG. Expression of pro/anti-inflammatory macrophage markers was analyzed. Adhesion of monocytes as well as oxidative stress status, viability, and TGF-β expression after primary aortic cell exposure to macrophage-conditioned medium with and without PGG were assessed. The release of TGF-β was also examined in elastase-treated cultured rat aortas. Results: PGG pre-treatment of human aortic cell monolayers reduced the adhesion of THP-1 monocytes. PGG enhanced the expression of anti-inflammatory markers in THP-1-derived macrophages, and increased mitochondrial reactive oxygen species as well as mitochondrial polarization. Conditioned medium from THP-1-derived macrophages induced reactive oxygen species, cell death, and TGF-β release from human aortic cells, which was suppressed by PGG. In explanted rat aortas, PGG reduced elastase mediated TGF-β release. Conclusions: Combining anti-inflammatory, cytotoxic, and oxidative effects, PGG has high cardiovascular therapeutic potential. We confirmed previous in vivo observations whereby PGG suppressed TGF-β response associated with disease resolution.
摘要：
背景：五格积酰葡萄糖（PGG）是一种具有血管保护特性的多酚。PGG的靶向递送逆转了几种啮齿动物模型中与巨噬细胞数量减少和转化生长因子-β（TGF-β）表达相关的主动脉瘤生长。因此，我们试图确定PGG降低巨噬细胞诱导的主动脉致病性的细胞机制及其与TGF-β的关系。方法:使用THP-1细胞,原代人主动脉细胞，移植了大鼠主动脉，我们评估了PGG的抗炎作用。分析促炎/抗炎巨噬细胞标志物的表达。单核细胞的粘附以及氧化应激状态，生存能力，在有和没有PGG的情况下，评估了原发性主动脉细胞暴露于巨噬细胞条件培养基后的TGF-β表达。还在弹性蛋白酶处理的培养的大鼠主动脉中检查了TGF-β的释放。结果：PGG预处理人主动脉细胞单层降低了THP-1单核细胞的粘附。PGG增强THP-1源性巨噬细胞抗炎标志物的表达,和增加线粒体活性氧以及线粒体极化。来自THP-1衍生的巨噬细胞的条件培养基诱导的活性氧，细胞死亡,和TGF-β从人主动脉细胞释放，被PGG压制。在移植的大鼠主动脉中，PGG降低了弹性蛋白酶介导的TGF-β释放。结论：联合抗炎，细胞毒性，和氧化作用，PGG具有很高的心血管治疗潜力。我们证实了先前的体内观察结果，即PGG抑制了与疾病消退相关的TGF-β反应。
