Objective:

To elucidate the molecular mechanisms of vascular wall-mediated mechanopriming and endothelial mechanotransduction in atherosclerosis.

Approach:

• Mechanistic Insights: The review discusses the role of Piezo1 ion channel and 5-HT1B receptor as coincidence detectors integrating fluid shear stress and matrix stiffness signals.
• Pathological Reprogramming: It highlights how dysregulation of mechanopathways leads to endothelial cell senescence, pyroptosis, and endothelial-to-mesenchymal transition.
• Clinical Applications: The integration of multimodal imaging and computational fluid dynamics for quantifying wall shear stress is explored.
• Future Directions: The review proposes shear stress-targeted therapeutic strategies and a precision cardiovascular medicine framework.

Key Findings:

• Atherosclerosis exhibits a focal distribution at arterial bifurcations and curvatures, indicating that systemic risk factors alone do not explain its pathogenesis.
• Disturbed flow and oscillatory shear stress are critical mechanical drivers of plaque progression.
• Low shear stress and OSS promote plaque growth and pathological remodeling, while high shear stress influences plaque vulnerability.
• Current clinical risk stratification models may benefit from incorporating localized hemodynamic parameters.

Interpretation:

Limitations:

• The review primarily focuses on mechanobiological mechanisms without extensive clinical trial data to support the proposed therapeutic strategies.
• Further research is needed to validate the clinical applicability of the discussed imaging and therapeutic approaches.

Conclusion: