Department of Bioengineering, Clemson University, Clemson, SC, USA.
Department of Bioengineering, Clemson University, Clemson, SC, USA.
Biochem Biophys Res Commun. 2014 Feb 7;444(2):205-11. doi: 10.1016/j.bbrc.2014.01.027. Epub 2014 Jan 16.
Abdominal aortic aneurysms (AAA) are progressive dilatations of infra-renal aorta causing structural weakening rendering the aorta prone to rupture. AAA can be potentially stabilized by inhibiting inflammatory enzymes such as matrix metalloproteinases (MMP); however, active regression of AAA is not possible without new elastic fiber regeneration. Here we report the elastogenic benefit of direct delivery of polyphenols such as pentagalloyl glucose (PGG), epigallocatechin gallate (EGCG), and catechin, to smooth muscle cells obtained either from healthy or from aneurysmal rat aorta. Addition of 10 μg/ml PGG and ECGC induce elastin synthesis, organization, and crosslinking while catechin does not. Our results indicate that polyphenols bind to monomeric tropoelastin and enhance coacervation, aid in crosslinking of elastin by increasing lysyl oxidase (LOX) synthesis, and by blocking MMP-2 activity. Thus, polyphenol treatments leads to increased mature elastin fibers synthesis without increasing the production of intracellular tropoelastin.
腹主动脉瘤 (AAA) 是肾下主动脉的进行性扩张，导致结构弱化，使主动脉易于破裂。通过抑制基质金属蛋白酶 (MMP) 等炎症酶，AAA 可以得到潜在的稳定；然而，如果没有新的弹性纤维再生，AAA 就不可能发生主动消退。在这里，我们报告了将多酚（如五没食子酰葡萄糖 (PGG)、表没食子儿茶素没食子酸酯 (EGCG) 和儿茶素）直接递送至从健康或动脉瘤大鼠主动脉获得的平滑肌细胞的弹性生成益处。添加 10 μg/ml 的 PGG 和 ECGC 可诱导弹性蛋白的合成、组织和交联，而儿茶素则不能。我们的结果表明，多酚与单体原弹性蛋白结合，增强凝聚，并通过增加赖氨酰氧化酶 (LOX) 合成和抑制 MMP-2 活性，有助于弹性蛋白的交联。因此，多酚处理会导致成熟弹性纤维合成增加，而不会增加细胞内原弹性蛋白的产生。
