Endotoxinemia Accelerates Atherosclerosis Through Electrostatic Charge-Mediated Monocyte Adhesion.

Area of Science:

• Cardiovascular Research
• Immunology
• Microbiology

Background:

• Acute infections are known risk factors for cardiovascular inflammation and complications.
• The precise mechanisms linking infection to exacerbated cardiovascular disease remain unclear.
• Lipopolysaccharide (LPS) from Gram-negative bacteria activates immune cells like neutrophils, releasing neutrophil extracellular traps (NETs) that promote inflammation.

Purpose of the Study:

• To investigate how acute infection and subsequent neutrophil activation accelerate vascular inflammation.
• To elucidate the role of NETs in the context of atherosclerosis during endotoxemia.

Main Methods:

• Acute infection was modeled using lipopolysaccharide injection in hypercholesterolemic mice.
• Atherosclerosis progression was assessed via histomorphometry of the aortic root.
• Arterial myeloid cell adhesion was quantified using intravital microscopy and in vitro assays.

Main Results:

• LPS treatment increased atherosclerotic lesion size and myeloid cell accumulation.
• NET deposition along the arterial lumen was observed, and NET inhibition reduced lesion expansion.
• Histone H2a within NETs was identified as a key mediator attracting monocytes in a charge-dependent manner.

Conclusions:

• NET-associated histone H2a drives charge-dependent monocyte adhesion to NETs.
• This process accelerates atherosclerosis during acute endotoxemia.
• Targeting histone H2a offers a potential therapeutic strategy to mitigate infection-induced cardiovascular complications.