Estrada Rosendo, Giridharan Guruprasad, Prabhu Sumanth D, Sethu Palaniappan
Department of Bioengineering, Speed School of Engineering, University of Louisville, Louisville, KY, USA.
Annu Int Conf IEEE Eng Med Biol Soc. 2011;2011:186-9. doi: 10.1109/IEMBS.2011.6089925.
Atherosclerotic lesions form non-randomly at locations in bends and bifurcations where the local flow can be classified as 'disturbed flow' and is associated with low shear stress oscillatory or reciprocating flow. Endothelial cells in vivo are constantly exposed to mechanical stimulation due to hemodynamic loading in the form of pulsatile pressure, cyclic stretch and shear stress to maintain phenotype and control function. In conditions like atherosclerosis, the pressure and strain loading remains the same whereas the local fluid flow behavior and shear stress are altered. Common in vitro models of atherosclerosis focus primarily on shear stress without accounting for pressure and strain loading. To overcome this limitation, we used our microfluidic Endothelial Cell Culture Model (ECCM) to achieve accurate replication of pressure, strain and shear stress waveforms associated with both normal flow seen in straight sections of arteries and disturbed flow seen atherosclerosis lesion susceptible regions. We specifically recreated mechanical stresses associated with the proximal internal carotid which is a major risk factor for stroke. Cells cultured using both conditions show distinct differences in alignment and cytoskeletal organization. In summary we recreated pressure, stretch and shear stress loading seen in straight sections and in the proximal internal carotid in a cell culture compatible platform.
动脉粥样硬化病变非随机地形成于血管弯曲和分支处，这些部位的局部血流可归类为“紊乱血流”，并与低剪切应力、振荡或往复血流相关。体内的内皮细胞由于脉动压力、周期性拉伸和剪切应力形式的血流动力学负荷而不断受到机械刺激，以维持其表型并控制功能。在动脉粥样硬化等病症中，压力和应变负荷保持不变，而局部流体流动行为和剪切应力发生改变。常见的动脉粥样硬化体外模型主要关注剪切应力，而未考虑压力和应变负荷。为克服这一局限性，我们使用了微流控内皮细胞培养模型（ECCM），以准确复制与动脉直管段中的正常血流以及动脉粥样硬化病变易感区域中的紊乱血流相关的压力、应变和剪切应力波形。我们特别重现了与颈内动脉近端相关的机械应力，颈内动脉近端是中风的主要危险因素。在这两种条件下培养的细胞在排列和细胞骨架组织方面表现出明显差异。总之，我们在一个细胞培养兼容平台上重现了直管段和颈内动脉近端中所见的压力、拉伸和剪切应力负荷。
