Extracellular peroxiredoxin 5 exacerbates atherosclerosis via the TLR4/MyD88 pathway

Area of Science:

• Cardiovascular Biology
• Immunology
• Oxidative Stress Research

Background:

• Atherosclerosis involves inflammation and oxidative stress, with Peroxiredoxin 5 (PRDX5) implicated in regulating these processes.
• The specific role of PRDX5 in atherosclerosis pathogenesis, particularly in vascular endothelial dysfunction, remains largely undefined.

Purpose of the Study:

• To investigate the role of PRDX5 in the development and progression of atherosclerosis.
• To elucidate the underlying molecular mechanisms by which PRDX5 influences vascular inflammation and plaque formation.

Main Methods:

• In vivo studies utilized 60-week-old Apolipoprotein E knockout (ApoE-/-) and Prdx5-/-; ApoE-/- mice on a normal chow diet.
• In vitro experiments involved stimulating human umbilical vein endothelial cells (HUVECs) with oxidized LDL (oxLDL) and assessing PRDX5 knockdown effects.
• Key signaling pathways, including TLR4/MyD88/NF-κB and P38, were analyzed.

Main Results:

• Atherosclerotic conditions showed elevated PRDX5 expression in both humans and mice.
• Prdx5-/-; ApoE-/- mice exhibited reduced plaque formation, macrophage accumulation, and vascular inflammation.
• PRDX5 knockdown in oxLDL-stimulated HUVECs decreased monocyte adhesion and migration, indicating reduced immune response.
• PRDX5 deficiency inhibited the TLR4/MyD88/NF-κB and P38 signaling pathways.

Conclusions:

• Extracellular PRDX5 exacerbates atherosclerosis by promoting endothelial inflammation and macrophage accumulation.
• PRDX5 activates the TLR4/MyD88/NF-κB and P38 signaling pathways, contributing to disease progression.
• Targeting extracellular PRDX5 may offer a novel therapeutic strategy for atherosclerosis.