Apurinic/apyrimidinic endonuclease1/redox factor-1 inhibits monocyte adhesion in endothelial cells

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Atherosclerosis Research

Background:

• Monocyte adhesion to endothelial cells is an early event in atherosclerosis.
• Apurinic/apyrmidinic endonuclease1/redox factor-1 (APE1/ref-1) is a key protein involved in DNA repair and gene regulation.
• The role of APE1/ref-1 in endothelial-monocyte interactions is not fully understood.

Purpose of the Study:

• To investigate the role of APE1/ref-1 in the interaction between monocytes and vascular endothelial cells.
• To determine the effect of APE1/ref-1 overexpression on monocyte adhesion and vascular cell adhesion molecule-1 (VCAM-1) expression.

Main Methods:

• Human umbilical vein endothelial cells (HUVECs) were transfected with an adenovirus encoding APE1/ref-1.
• Monocyte adhesion, VCAM-1 expression, and intracellular superoxide production were measured in TNF-alpha-activated HUVECs.
• The effect of nitric oxide synthase (NOS) inhibition on APE1/ref-1-mediated suppression was assessed.

Main Results:

• Overexpression of APE1/ref-1 suppressed U937 monocyte adhesion to TNF-alpha-stimulated HUVECs.
• APE1/ref-1 overexpression reduced TNF-alpha-induced VCAM-1 expression.
• This suppression was dependent on nitric oxide synthase (NOS) activity and involved inhibition of superoxide production and p38 MAPK phosphorylation.

Conclusions:

• APE1/ref-1 mitigates TNF-alpha-induced monocyte adhesion and VCAM-1 expression in endothelial cells.
• The anti-adhesive property of APE1/ref-1 is primarily mediated by a NOS-dependent mechanism.
• APE1/ref-1 may inhibit VCAM-1 expression by reducing superoxide production and p38 MAPK activation, offering a potential therapeutic target for atherosclerosis.