Haemodynamic Wall Shear Stress, Endothelial Permeability and Atherosclerosis-A Triad of Controversy

Area of Science:

• Cardiovascular Research
• Biomedical Engineering
• Pathophysiology

Background:

• Atherosclerosis exhibits a non-uniform distribution in arteries, suggesting localized risk factors.
• Hemodynamic forces, particularly wall shear stress (WSS), and endothelial permeability are implicated in lesion development.
• Controversies exist regarding lesion localization, hemodynamic triggers, lipid transport, and WSS effects on permeability.

Purpose of the Study:

• To review and critically evaluate current understanding of atherosclerosis lesion localization.
• To examine the role of wall shear stress (WSS) and endothelial permeability in atherogenesis.
• To present evidence for and against existing hypotheses and explore newer findings.

Main Methods:

• Literature review and critical analysis of existing studies on atherosclerosis.
• Evaluation of evidence concerning hemodynamic triggers (WSS) and endothelial function.
• Assessment of lipid transport mechanisms across the endothelium.

Main Results:

• The review challenges the consensus that low/oscillatory WSS solely drives lesion formation via widened junctions.
• Emerging evidence suggests lesion location shifts with age and multidirectional shear stress is crucial.
• Low-density lipoprotein (LDL) predominantly crosses the endothelium via transcytosis, mediated by shear-sensitive factors.

Conclusions:

• The established link between low WSS and atherosclerosis initiation needs re-evaluation.
• Multidirectional shear stress and transcytosis are likely key mechanisms in lesion development.
• Further research into shear-sensitive mediators is required to understand atherosclerosis pathogenesis.