Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana, United States of America.
PLoS One. 2013 Nov 22;8(11):e82456. doi: 10.1371/journal.pone.0082456. eCollection 2013.
Over the past 10 years, the number of percutaneous coronary intervention procedures performed in the United States increased by 33%; however, restenosis, which inhibits complete functional recovery of the vessel wall, complicates this procedure. A wide range of anti-restenotic therapeutics have been developed, although many elicit non-specific effects that compromise vessel healing. Drawing inspiration from biologically-relevant molecules, our lab developed a mimic of the natural proteoglycan decorin, termed DS-SILY, which can mask exposed collagen and thereby effectively decrease platelet activation, thus contributing to suppression of vascular intimal hyperplasia. Here, we characterize the effects of DS-SILY on both proliferative and quiescent human SMCs to evaluate the potential impact of DS-SILY-SMC interaction on restenosis, and further characterize in vivo platelet interactions. DS-SILY decreased proliferative SMC proliferation and pro-inflammatory cytokine secretion in vitro in a concentration dependent manner as compared to untreated controls. The addition of DS-SILY to in vitro SMC cultures decreased SMC migration and protein synthesis by 95% and 37%, respectively. Furthermore, DS-SILY decreased platelet activation, as well as reduced neointimal hyperplasia by 60%, in vivo using Ossabaw swine. These results indicate that DS-SILY demonstrates multiple biological activities that may all synergistically contribute to an improved treatment paradigm for balloon angioplasty.
在过去的 10 年中，美国进行的经皮冠状动脉介入治疗程序增加了 33%；然而，再狭窄会抑制血管壁的完全功能恢复，使该程序复杂化。尽管许多治疗方法会产生非特异性影响，从而损害血管愈合，但已经开发出了广泛的抗再狭窄治疗方法。受生物相关分子的启发，我们实验室开发了一种天然蛋白聚糖 decorin 的模拟物，称为 DS-SILY，它可以掩盖暴露的胶原蛋白，从而有效减少血小板激活，从而有助于抑制血管内膜增生。在这里，我们研究了 DS-SILY 对增殖和静止的人平滑肌细胞的影响，以评估 DS-SILY-SMC 相互作用对再狭窄的潜在影响，并进一步研究体内血小板相互作用。与未处理的对照组相比，DS-SILY 以浓度依赖的方式降低了体外增殖性平滑肌细胞的增殖和促炎细胞因子的分泌。DS-SILY 添加到体外平滑肌细胞培养物中，分别使 SMC 迁移和蛋白质合成减少 95%和 37%。此外，DS-SILY 在体内降低了 Ossabaw 猪的血小板激活和新生内膜增生 60%。这些结果表明，DS-SILY 表现出多种生物学活性，这些活性可能协同作用，为球囊血管成形术提供更好的治疗方案。
