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

Abstract

This study employs dissipative particle dynamics (DPD) to investigate low-density lipoprotein (LDL) transport across the endothelium under varying conditions of endothelial leakiness size, LDL concentration, and blood pressure. The endothelial gap size was found to strongly influence LDL transport efficiency: a 32.24 nm gap permitted approximately 1.2 times more LDL particles to cross than a 28.69 nm endothelial leakiness. Moreover, higher LDL concentrations significantly promoted transendothelial movement, with tenfold elevations in LDL levels increasing transport by about 1.6 times compared to baseline. Finally, elevated blood pressure more than doubled the number of LDL particles crossing the endothelium relative to normal pressure. These findings underscore the critical roles of endothelial integrity, lipid homeostasis, and blood pressure in the progression of atherosclerosis. Larger gaps, excessive LDL levels, and hypertension all contribute to heightened LDL infiltration, potentially accelerating plaque development. By elucidating these mechanisms at the mesoscopic scale, this research provides valuable insights into the interplay between endothelial permeability and cardiovascular risk factors. The results highlight the importance of strategies aimed at maintaining healthy lipid levels, preserving endothelial function, and controlling blood pressure to mitigate atherosclerosis.