The in vitro Effect of Oxidized LDL and PHA on Proliferation and Gene Expression of Regulatory T Cells in Patients with Atherosclerosis

Abstract

Atherosclerosis is a chronic inflammatory condition that affects the arterial wall. Oxidized low- density lipoprotein (ox-LDL) seems to have an important role in atherosclerotic plaque formation. This study was performed to investigate the effects of ox-LDL as well as PHA on proliferation and gene expression of peripheral blood mononuclear cells (PBMCs) in patients with atherosclerosis compared to healthy controls. Proliferation of PBMCs was assessed by BrdU assay, while gene expression was assessed by real-time PCR. Both PHA and ox-LDL significantly induced proliferation of PBMCs of patients and controls. PBMCs from controls showed significantly higher proliferation when stimulated with ox-LDL compared to patients. Expression of TGF-β was significantly lower in PBMCs from patients compared to healthy controls (p<0.001). Following simulation with PHA, TGF-β and Foxp3 gene expression levels in patients and controls were significantly decreased (p<0.001). Expression of Foxp3 in PBMCs treated with ox-LDL was significantly decreased in patients and controls. Decreased expression of TGF-β and Foxp3 genes after ox-LDL stimulation may be due to more sensitivity of Treg cells than effector T cells to ox-LDL. Presence of ox-LDL within atheroma could be associated with the diminished population of Treg cells in the atherosclerotic patients.

Keywords

• Atherosclerosis
• Gene expression
• Ox-LDL
• Peripheral blood mononuclear cells
• T regulatory cells