Coupled Modeling of Lipid Deposition, Inflammatory Response and Intraplaque Angiogenesis in Atherosclerotic Plaque

Abstract

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.

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