Early atherogenesis: In search of etiology

Area of Science:

• Cardiovascular Biology
• Pathology
• Biomedical Engineering

Background:

• Atherosclerosis is a complex chronic inflammatory disease affecting large arteries.
• Early atherogenesis involves endothelial dysfunction, lipoprotein modification, monocyte recruitment, and foam cell formation, leading to fatty streaks.
• Numerous molecular mediators and risk factors contribute to atherogenesis, but its precise etiology remains unclear.

Purpose of the Study:

• To review early atherogenic processes and their mediators.
• To explore the complexity and uncertainties in atherogenesis initiation.
• To evaluate evidence-based risk factors for atherosclerosis causation using established criteria.

Main Methods:

• Description of early atherogenic processes and key molecular mediators.
• Exploration of the complexity of atherogenesis and risk factor relationships.
• Application of causation criteria (temporality, strength, plausibility, experimental evidence) to identified risk factors.

Main Results:

• Early atherogenesis involves multiple molecular pathways and risk factors.
• The relationships between identified risk factors and atherogenic processes are complex and not fully understood.
• Disturbed wall shear stress is the only risk factor that substantially meets established criteria for causation of atherosclerosis.

Conclusions:

• While numerous factors contribute to atherosclerosis, disturbed wall shear stress emerges as a primary etiological factor.
• Understanding the causal role of disturbed hemodynamics offers insights into atherosclerosis development.
• Further research into wall shear stress implications may reveal new diagnostic and therapeutic targets.