Mass transport, atherogenesis, and risk

Area of Science:

• Cardiovascular Science
• Biomedical Engineering
• Transport Phenomena

Background:

• Atherosclerosis is a complex disease involving lipid accumulation in artery walls.
• The local concentration of atherogenic molecules (atherogens) is a key driver of lesion development.
• Understanding transport mechanisms is crucial for predicting atherosclerosis risk.

Purpose of the Study:

• To model the transport of atherogens across the arterial wall.
• To determine how transport processes influence local atherogen concentration (chemical activity).
• To evaluate the impact of various factors on atherosclerosis risk.

Main Methods:

• Developed a steady-state model for combined diffusive and convective transport of an atherogen.
• Simulated transport across a multilayered arterial wall.
• Assessed the effects of endothelial permeability, blood pressure, serum atherogen levels, internal elastica fenestration, and intimal thickening.

Main Results:

• Mild increases in endothelial permeability combined with interstitial sieving led to high local atherogen concentrations, increasing risk.
• Hypertension, elevated serum atherogen levels, and intimal thickening amplified risk only when endothelial junctions were compromised or sieving occurred.
• Traditional risk factors were ineffective without compromised endothelial junctions or interstitial sieving.

Conclusions:

• Transport processes, particularly endothelial permeability and interstitial sieving, are critical determinants of atherosclerosis risk.
• These transport mechanisms can dictate lesion architecture and development rate.
• The model explains known and previously puzzling observations in atherosclerosis research.