Acampora K Bethany, Nagatomi Jiro, Langan Eugene M, LaBerge Martine
Department of Bioengineering, Clemson University, 301 Rhodes Hall, Clemson, SC 29634, USA.
Ann Vasc Surg. 2010 Jan;24(1):116-26. doi: 10.1016/j.avsg.2009.07.019. Epub 2009 Sep 24.
Restenosis remains a common problem following balloon angioplasty, and it has been speculated that changes in the mechanical environment due to endovascular interventions are correlated with shifts in smooth muscle cell (SMC) phenotype. In order to study SMC response to forces similar to those exerted during balloon angioplasty, an in vitro concurrent shear and tensile forces simulator has been developed. After 24 hr of exposure to cyclic tension (5%) and shear (0.1-0.5 dynes/cm(2)) following simulated angioplasty injury (12% stretch), rat aortic SMCs exhibited significant synthetic behavior. These responses included increased cell proliferation, apoptosis, and cell hypertrophy compared to cells exposed to strain alone. While all SMCs exposed to dynamic stimuli (strain, strain+balloon injury, strain+balloon injury+shear) demonstrated a decrease in contractile protein expression, the injury group also exhibited significantly greater expression of the synthetic marker vimentin. These in vitro findings agree with in vivo events following balloon angioplasty and present a refined dynamic model to be implemented for better understanding of SMC activation and prevention of responses through pharmacological treatment.
再狭窄仍是球囊血管成形术后常见的问题,据推测,血管内介入导致的机械环境变化与平滑肌细胞(SMC)表型转变相关。为了研究SMC对类似于球囊血管成形术期间所施加力的反应,已开发出一种体外同时施加剪切力和拉伸力的模拟器。在模拟血管成形术损伤(12%拉伸)后,对大鼠主动脉SMC施加24小时的循环张力(5%)和剪切力(0.1 - 0.5达因/平方厘米),与仅暴露于应变的细胞相比,这些SMC表现出显著的合成行为。这些反应包括细胞增殖、凋亡和细胞肥大增加。虽然所有暴露于动态刺激(应变、应变 + 球囊损伤、应变 + 球囊损伤 + 剪切)的SMC收缩蛋白表达均降低,但损伤组合成标志物波形蛋白的表达也显著更高。这些体外研究结果与球囊血管成形术后的体内情况相符,并提出了一个完善的动态模型,以便更好地理解SMC激活以及通过药物治疗预防相关反应。