School of Biological Sciences and Medical Engineering, Southeast University, Nanjing, 210096, China.
School of Chemistry, Physics and Mechanical Engineering, Queensland University of Technology, Brisbane, QLD, 4001, Australia.
Ann Biomed Eng. 2019 Feb;47(2):439-452. doi: 10.1007/s10439-018-02173-1. Epub 2018 Nov 28.
We propose a multiphysical mathematical model by fully coupling lipid deposition, monocytes/macrophages recruitment and angiogenesis to investigate the pathophysiological responses of an atherosclerotic plaque to the dynamic changes in the microenvironment. The time evolutions of cellular (endothelial cells, macrophages, smooth muscle cells, etc.) and acellular components (low density lipoprotein, proinflammatory cytokines, extravascular plasma concentration, etc.) within the plaque microenvironment are assessed quantitatively. The thickening of the intima, the distributions of the lipid and inflammatory factors, and the intraplaque hemorrhage show a qualitative consistency with the MRI and histology data. Models with and without angiogenesis are compared to demonstrate the important role of neovasculature in the accumulation of blood-borne components in the atherosclerotic lesion by extravasation from the leaky vessel wall, leading to the formation of a lipid core and an inflammatory microenvironment, which eventually promotes plaque destabilization. This model can serve as a theoretical platform for the investigation of the pathological mechanisms of plaque progression and may contribute to the optimal design of atherosclerosis treatment strategies, such as lipid-lowering or anti-angiogenetic therapies.
我们提出了一个多物理数学模型，通过完全耦合脂质沉积、单核细胞/巨噬细胞募集和血管生成，来研究动脉粥样硬化斑块对微环境动态变化的病理生理反应。斑块微环境中细胞（内皮细胞、巨噬细胞、平滑肌细胞等）和无细胞成分（低密度脂蛋白、促炎细胞因子、血管外血浆浓度等）的时间演变被定量评估。内膜增厚、脂质和炎症因子的分布以及斑块内出血与 MRI 和组织学数据具有定性一致性。比较有和没有血管生成的模型，以证明新生血管在通过渗漏的血管壁从血液中渗出的富含血液的成分在动脉粥样硬化病变中的积累中的重要作用，导致脂质核心和炎症微环境的形成，最终促进斑块不稳定。该模型可以作为研究斑块进展病理机制的理论平台，并有助于优化动脉粥样硬化治疗策略的设计，如降脂或抗血管生成治疗。
