Combining Inflammation and Tissue Turnover in the Modeling of Atherosclerosis Development Following the Outside-In...

Area of Science:

• Biomedical Engineering
• Computational Biology
• Cardiovascular Research

Background:

• Atherosclerosis is a leading cause of cardiovascular disease, with unclear mechanisms of lesion development.
• The vasa vasorum (VV), small vessels in artery walls, are increasingly implicated in disease initiation via an 'outside-in' mechanism.
• Perfusion deficits in VV may trigger inflammation and plaque formation in arterial walls.

Purpose of the Study:

• To develop and validate a novel computational model for atherosclerosis.
• To investigate the role of vasa vasorum dysfunction in disease progression.
• To elucidate the coupled interactions between transport, inflammation, and mechanics in arterial wall remodeling.

Main Methods:

• A multi-field computational model integrating tissue turnover, inflammation (phase-field), and growth (kinematics).
• Governed perfusion using a diffusion-reaction equation, incorporating VV dysfunction.
• Employed the finite element method for numerical implementation and assessed through case studies.

Main Results:

• Simulation results demonstrate the coupled effects of blood-borne factors, inflammation, and mechanics.
• Compromised VV function initiates a cycle of ischemia, inflammation, and plaque growth.
• Increased blood pressure correlates with elevated stress in atherosclerotic plaque tissue.

Conclusions:

• The model provides insights into the outside-in mechanism of atherosclerosis driven by VV dysfunction.
• Highlights the critical interplay between vascular mechanics, inflammation, and tissue turnover.
• Model predictions require future validation, acknowledging inherent approximations.