Mesoscopic Insights Into Low-Density Lipoprotein Transport: A Dissipative Particle Dynamics Study

Area of Science:

• Biophysics
• Cardiovascular Science
• Computational Biology

Background:

• Atherosclerosis is a complex disease involving lipid accumulation in artery walls.
• Endothelial dysfunction plays a critical role in the initiation and progression of atherosclerosis.
• Understanding the dynamics of low-density lipoprotein (LDL) transport across the endothelium is crucial for disease prevention and treatment.

Purpose of the Study:

• To investigate the impact of endothelial leakiness, LDL concentration, and blood pressure on LDL transport across the endothelium using dissipative particle dynamics (DPD).
• To quantify the relationship between varying physiological parameters and the efficiency of LDL particle transmigration.

Main Methods:

• Dissipative Particle Dynamics (DPD) simulations were employed to model LDL transport.
• Simulations were conducted under varied conditions of endothelial gap size, LDL concentration, and blood pressure.
• Quantitative analysis of LDL particle flux across the simulated endothelial barrier was performed.

Main Results:

• Endothelial gap size significantly influences LDL transport; a larger gap (32.24 nm) allowed ~1.2 times more LDL particles than a smaller gap (28.69 nm).
• Elevated LDL concentrations markedly increased trans-endothelial movement, with a tenfold increase in LDL levels boosting transport ~1.6 times baseline.
• Increased blood pressure more than doubled the number of LDL particles crossing the endothelium compared to normal pressure.

Conclusions:

• Endothelial integrity, lipid homeostasis, and blood pressure are critical determinants of LDL infiltration.
• Larger endothelial gaps, high LDL levels, and hypertension collectively promote LDL accumulation in the arterial wall.
• These factors are key contributors to the acceleration of atherosclerotic plaque development.