Unit of Medical Technology and Intelligent Information Systems, Department of Materials Science and Engineering, University of Ioannina, Ioannina, Greece.
Am J Physiol Heart Circ Physiol. 2013 Jun 1;304(11):H1455-70. doi: 10.1152/ajpheart.00539.2012. Epub 2013 Mar 15.
Atherosclerosis is a systemic disease with local manifestations. Low-density lipoprotein (LDL) accumulation in the subendothelial layer is one of the hallmarks of atherosclerosis onset and ignites plaque development and progression. Blood flow-induced endothelial shear stress (ESS) is causally related to the heterogenic distribution of atherosclerotic lesions and critically affects LDL deposition in the vessel wall. In this work we modeled blood flow and LDL transport in the coronary arterial wall and investigated the influence of several hemodynamic and biological factors that may regulate LDL accumulation. We used a three-dimensional model of a stenosed right coronary artery reconstructed from angiographic and intravascular ultrasound patient data. We also reconstructed a second model after restoring the patency of the stenosed lumen to its nondiseased state to assess the effect of the stenosis on LDL accumulation. Furthermore, we implemented a new model for LDL penetration across the endothelial membrane, assuming that endothelial permeability depends on the local lumen LDL concentration. The results showed that the presence of the stenosis had a dramatic effect on the local ESS distribution and LDL accumulation along the artery, and areas of increased LDL accumulation were observed in the downstream region where flow recirculation and low ESS were present. Of the studied factors influencing LDL accumulation, 1) hypertension, 2) increased endothelial permeability (a surrogate of endothelial dysfunction), and 3) increased serum LDL levels, especially when the new model of variable endothelial permeability was applied, had the largest effects, thereby supporting their role as major cardiovascular risk factors.
动脉粥样硬化是一种具有局部表现的全身性疾病。低密度脂蛋白（LDL）在血管内皮下层的积聚是动脉粥样硬化发病的标志之一，它引发了斑块的发展和进展。血流诱导的内皮剪切力（ESS）与动脉粥样硬化病变的异质性分布有因果关系，并对 LDL 在血管壁中的沉积有重要影响。在这项工作中，我们对冠状动脉壁中的血流和 LDL 转运进行了建模，并研究了几种可能调节 LDL 积聚的血液动力学和生物学因素的影响。我们使用了从血管造影和血管内超声患者数据重建的狭窄右冠状动脉的三维模型。我们还重建了狭窄管腔恢复到非病变状态后的第二个模型，以评估狭窄对 LDL 积聚的影响。此外，我们实现了一个 LDL 穿透内皮膜的新模型，假设内皮通透性取决于局部管腔 LDL 浓度。结果表明，狭窄的存在对局部 ESS 分布和动脉内 LDL 积聚有显著影响，并且在存在流动再循环和低 ESS 的下游区域观察到 LDL 积聚增加的区域。在所研究的影响 LDL 积聚的因素中，1）高血压，2）增加的内皮通透性（内皮功能障碍的替代物），以及 3）增加的血清 LDL 水平，尤其是当应用可变内皮通透性的新模型时，具有最大的影响，从而支持它们作为主要心血管危险因素的作用。
