School of Mechanical and Manufacturing Engineering, Dublin City University, Dublin 9, Ireland.
Biomech Model Mechanobiol. 2013 Aug;12(4):671-83. doi: 10.1007/s10237-012-0433-4. Epub 2012 Sep 8.
The putative effects of changes in mean strain and cyclic strain amplitude on vascular smooth muscle cell (vSMC) growth (proliferation and apoptosis) were examined. Subsequently, a quantitative measure of vSMC growth was obtained to determine the prolonged effect of changes in mechanical burden following bare-metal stent (BMS) and sirolimus drug-eluting stent (DES) deployment in vitro. Bovine aortic vSMCs were exposed to prolonged cyclic strain using a Flexercell(TM) Tension system and a novel Sylgard(TM) phantom vessel following stent implantation before the level of vSMC proliferation and apoptosis was assessed by FACS analysis, cell counting, and immunocytochemistry. Physiological cyclic strain (5%) decreased vSMC proliferation and increased apoptosis in a temporal manner. There was no significant difference in cell growth following exposure to varying mean strains with similar amplitude. In contrast, exposure to varying strain amplitudes with similar mean strains resulted in significant differences in cell proliferation and apoptosis. In parallel studies, the level of vSMC proliferation and cell survival was significantly increased within low amplitude, high mean strain regions of a phantom vessel following BMS implantation when compared to regions of higher strain amplitude upstream and downstream of the stent, respectively. Moreover, the level of vSMC growth within the stented region was significantly attenuated following implantation of a sirolimus-coated DES independent of significant changes in cell survival. Cyclic strain amplitude is an important regulator of vSMC growth capacity within a stent and is a target for inhibition using a sirolimus-coated DES.
研究了平均应变和循环应变幅度变化对血管平滑肌细胞(VSMC)生长(增殖和凋亡)的潜在影响。随后,通过体外检测裸金属支架(BMS)和西罗莫司药物洗脱支架(DES)植入后机械负荷变化的长期影响,获得了 VSMC 生长的定量测量。在支架植入后,使用 Flexercell(TM)张力系统和新型 Sylgard(TM)幻影血管,使牛主动脉 VSMC 长时间暴露于循环应变下,然后通过 FACS 分析、细胞计数和免疫细胞化学评估 VSMC 增殖和凋亡的水平。生理循环应变(5%)以时间依赖性方式降低 VSMC 增殖并增加凋亡。暴露于具有相似幅度的不同平均应变下,细胞生长没有显著差异。相比之下,暴露于具有相似平均应变的不同应变幅度会导致细胞增殖和凋亡的显著差异。在平行研究中,与支架上下游的高应变幅度区域相比,BMS 植入后,在幻影血管的低幅度、高平均应变区域,VSMC 增殖和细胞存活率显著增加。此外,在植入西罗莫司涂层 DES 后,支架区域内的 VSMC 生长水平显著降低,而细胞存活率没有明显变化。循环应变幅度是支架内 VSMC 生长能力的重要调节因子,可通过西罗莫司涂层 DES 抑制。