Atherosclerotic Plaque Crystals Induce Endothelial Dysfunction.

Area of Science:

• Vascular Biology
• Immunology
• Crystallization in Disease

Background:

• Endothelial dysfunction is a critical early step in atherosclerosis.
• The specific roles of endogenous crystals, such as cholesterol crystals (CC) and monosodium urate (MSU), in endothelial activation are not fully understood.

Purpose of the Study:

• To investigate the impact of CC and MSU on endothelial cells.
• To assess inflammatory signaling, mitochondrial respiration, and neutrophil recruitment in response to crystalline stimuli.

Main Methods:

• Human umbilical vein endothelial cells were exposed to CC and MSU in dose- and time-controlled experiments.
• Analysis included inflammatory signaling pathways (NF-κB, STAT3), cytokine profiles, mitochondrial respiration, and neutrophil adhesion assays.

Main Results:

• CC and MSU were internalized by endothelial cells, activating NF-κB and STAT3 pathways.
• Crystals induced pro-inflammatory cytokines and impaired mitochondrial respiration, particularly CC.
• Crystal stimulation and conditioned media promoted endothelial adhesion molecule expression and neutrophil adhesion.

Conclusions:

• Crystalline stimuli act as potent vascular danger signals, inducing endothelial inflammation and mitochondrial dysfunction.
• These crystal-induced responses contribute to vascular inflammation and immune cell engagement, hallmarks of early atherogenesis.
• The study provides mechanistic insights into crystal-driven vascular dysfunction in the early stages of atherosclerosis.