Atherosclerosis is characterised by the growth of fatty plaques in the inner artery wall. In mature plaques, vascular smooth muscle cells (SMCs) are recruited from adjacent tissue to deposit a collagenous cap over the fatty plaque core. This cap isolates the thrombogenic plaque content from the bloodstream and prevents the clotting cascade that leads to myocardial infarction or stroke. Despite the protective role of the cap, the mechanisms that regulate cap formation and maintenance are not well understood. It remains unclear why some caps become stable, while others become vulnerable to rupture. We develop a multiphase PDE model with non-standard boundary conditions to investigate collagen cap formation by SMCs in response to diffusible growth factor signals from the endothelium. Platelet-derived growth factor stimulates SMC migration, proliferation and collagen degradation, while transforming growth factor (TGF)-\(\beta \) stimulates SMC collagen synthesis and inhibits collagen degradation. The model SMCs respond haptotactically to gradients in the collagen phase and have reduced rates of migration and proliferation in dense collagenous tissue. The model, which is parameterised using in vivo and in vitro experimental data, reproduces several observations from plaque growth in mice. Numerical and analytical results demonstrate that a stable cap can be formed by a relatively small SMC population and emphasise the critical role of TGF-\(\beta \) in effective cap formation. These findings provide unique insight into the mechanisms that may lead to plaque destabilisation and rupture. This work represents an important step towards the development of a comprehensive in silico plaque model.

动脉粥样硬化的特征在于内动脉壁中脂肪斑的生长。在成熟斑块中，从相邻组织中募集血管平滑肌细胞（SMC），以在脂肪斑块核心上沉积胶原帽。该帽可将血栓中的血栓斑块隔离开，并防止导致心肌梗塞或中风的凝血级联反应。尽管瓶盖具有保护作用，但对瓶盖形成和维护的调节机制仍知之甚少。尚不清楚为什么有些瓶盖变得稳定，而另一些瓶盖容易破裂。我们开发了具有非标准边界条件的多相PDE模型，以研究SMC响应内皮中可扩散的生长因子信号而形成的胶原蛋白帽。血小板衍生的生长因子刺激SMC迁移，β刺激SMC胶原蛋白合成并抑制胶原蛋白降解。模型SMC对胶原相中的梯度进行触觉反应，并且在致密胶原组织中的迁移和增殖速率降低。使用体内和体外实验数据对模型进行参数化，可以从小鼠斑块生长中复制一些观察结果。数值和分析结果表明，可以由相对较小的SMC群体来形成稳定的瓶盖，并强调TGF-β （β）在有效瓶盖形成中的关键作用。这些发现为可能导致斑块不稳定和破裂的机制提供了独特的见解。这项工作代表了开发全面的计算机菌斑模型的重要一步。