School of Biological Sciences and Medical Engineering, Southeast University, Nanjing Jiangsu, China.
The Cardiovascular Research Foundation, New York, New York, United States of America.
PLoS Comput Biol. 2021 Mar 29;17(3):e1008344. doi: 10.1371/journal.pcbi.1008344. eCollection 2021 Mar.
Atherosclerotic plaque rupture is responsible for a majority of acute vascular syndromes and this study aims to develop a prediction tool for plaque progression and rupture. Based on the follow-up coronary intravascular ultrasound imaging data, we performed patient-specific multi-physical modeling study on four patients to obtain the evolutional processes of the microenvironment during plaque progression. Four main pathophysiological processes, i.e., lipid deposition, inflammatory response, migration and proliferation of smooth muscle cells (SMCs), and neovascularization were coupled based on the interactions demonstrated by experimental and clinical observations. A scoring table integrating the dynamic microenvironmental indicators with the classical risk index was proposed to differentiate their progression to stable and unstable plaques. The heterogeneity of plaque microenvironment for each patient was demonstrated by the growth curves of the main microenvironmental factors. The possible plaque developments were predicted by incorporating the systematic index with microenvironmental indicators. Five microenvironmental factors (LDL, ox-LDL, MCP-1, SMC, and foam cell) showed significant differences between stable and unstable group (p < 0.01). The inflammatory microenvironments (monocyte and macrophage) had negative correlations with the necrotic core (NC) expansion in the stable group, while very strong positive correlations in unstable group. The inflammatory microenvironment is strongly correlated to the NC expansion in unstable plaques, suggesting that the inflammatory factors may play an important role in the formation of a vulnerable plaque. This prediction tool will improve our understanding of the mechanism of plaque progression and provide a new strategy for early detection and prediction of high-risk plaques.
动脉粥样硬化斑块破裂是大多数急性血管综合征的原因，本研究旨在开发一种用于预测斑块进展和破裂的工具。基于对四名患者的后续冠状动脉血管内超声成像数据，我们进行了针对个体患者的多物理建模研究，以获得斑块进展过程中微环境的演化过程。基于实验和临床观察表明的相互作用，将四个主要的病理生理过程，即脂质沉积、炎症反应、平滑肌细胞（SMC）的迁移和增殖以及新生血管形成进行了耦合。提出了一个整合动态微环境指标与经典风险指数的评分表，以区分它们向稳定和不稳定斑块的进展。通过主要微环境因素的生长曲线，证明了每位患者斑块微环境的异质性。通过将系统指数与微环境指标相结合，预测了可能的斑块发展。五个微环境因素（LDL、氧化型 LDL、MCP-1、SMC 和泡沫细胞）在稳定组和不稳定组之间表现出显著差异（p < 0.01）。在稳定组中，炎症微环境（单核细胞和巨噬细胞）与坏死核心（NC）扩张呈负相关，而在不稳定组中呈非常强的正相关。炎症微环境与不稳定斑块中 NC 扩张强烈相关，提示炎症因子可能在易损斑块的形成中起重要作用。该预测工具将提高我们对斑块进展机制的理解，并为高危斑块的早期检测和预测提供新策略。
