Endothelial shear stress signal transduction and atherogenesis: From mechanisms to therapeutics

Area of Science:

• Cardiovascular Biology
• Mechanobiology
• Cellular Pathophysiology

Background:

• Atherosclerotic vascular disease is a leading global cause of mortality.
• Atherosclerotic plaques preferentially form at arterial sites with low or disturbed shear stress.
• Endothelial cell responses to shear stress are critical in atherosclerosis initiation and progression.

Purpose of the Study:

• To review recent advances in endothelial mechano-transduction.
• To elucidate the role of endothelial mechano-transduction in atherosclerosis pathogenesis.
• To highlight therapeutic strategies targeting mechano-regulated signaling.

Main Methods:

• Review of existing literature on endothelial cell biology and atherosclerosis.
• Analysis of mechano-sensitive signaling pathways in endothelial cells.
• Synthesis of current understanding of shear stress effects on vascular endothelium.

Main Results:

• Oscillatory shear stress induces diverse endothelial cell phenotypic changes (inflammation, oxidative stress, apoptosis, etc.).
• Mechano-sensors, adaptor proteins, kinases, and transcription factors mediate shear stress signal transduction.
• These pathways control gene expression, influencing endothelial cell fate and atherosclerotic lesion development.

Conclusions:

• Endothelial mechano-transduction is fundamental to atherosclerosis pathogenesis.
• Targeting mechano-regulated signaling pathways presents promising therapeutic avenues for atherosclerotic vascular disease.
• Further understanding of these cascades can lead to novel anti-atherosclerosis strategies.