(707.8) Understanding the Development of Atherosclerosis: Computational Model Depicting the Interaction Between Low-Density Lipoproteins and Vascular Calcification

Poster Board Number: E19

Nina Kosciuszek (New York Institute of Technology College of Osteopathic Medicine), Gorg Megalaa (New York Institute of Technology College of Osteopathic Medicine), Olga Savinova (New York Institute of Technology College of Osteopathic Medicine)

Objective: Cardiovascular disease (CVD) affects many individuals in the United States each year. It has many modifiable risk factors, such as hyperlipidemia and hypertension. Another risk factor is vascular calcification, which has been shown to be an independent risk factor in mortality in patients with CVD. Vascular calcification and the number of circulating low-density lipoprotein (LDL) particles influence atherosclerotic plaque formation and progression. However, the interaction between calcification and atherosclerosis is not completely understood.

Hypothesis: We have previously shown that vascular calcification modifies the endothelial surface topology, thus altering the amount of wall shear stress (WSS) present against the arterial wall. Therefore, we hypothesize that more LDL particles will approximate near the arterial wall, specifically in areas exhibiting low WSS. We postulate that vascular calcification influences LDL particle accumulation near the arterial wall, hence contributing to the pathogenesis of atherosclerosis.

Methods: As previously reported, we created a Fluid Structure Interaction (FSI) model from abdominal aorta geometries that were reconstructed from micro-CT images at 5.7 µm resolution. One geometry was from mico-CT images of a mouse that were genetically modified to have microcalcifications within the subendothelial layer (affected). In contrast, a mouse that was not genetically modified served as the control aorta geometry (control). This FSI model considered a nonlinear structure and hyperplastic materials in a steady-state phase. A Particle Tracing module was added to this model in COMSOL Multiphysics 5.6 (COMSOL Inc.). This allowed for the examination of the behavior of 2,100 LDL particles in relation to the rough and smooth surfaces of the affected and control aortas.

Results: The larger curvature of the affected aorta contained the greatest quantity of calcified lesions. This curvature demonstrated more LDL particles accumulating near the interior wall compared to the larger curvature of a healthy aorta. It was observed that the aorta with the calcified nodules experience a lower magnitude of WSS compared to the control aorta. It was observed that the particles clustered in areas that exhibited low WSS, ranging from less than 10 N/m2 in the affected aorta.

Conclusions: Rougher surface topology of a calcified aorta illustrates a positive correlation with LDL particle accumulation in the areas of low WSS. This provides insight to how WSS and vascular calcification influence atherosclerotic plaque formation and progression based on the behavior of LDL particles in this model. Further work needs to be done to explore other material properties to better simulate and understand this interaction.

Support or Funding Information

This work was supported in part by the National Institutes of Health grant R01HL149864 (OVS) and the NYITCOM Academic Medicine Scholar Program (NDK).