BACH2Functions Suppressed By Oxidized Low Density Lipoprotein (Ox-LDL) In Patients With Acute Coronary Syndrome

Background/Aims:We investigated the effect of oxidized low-density lipoprotein (ox-LDL) on expression levels of B lymphoid transcription repressor BTB and CNC homology2(BACH2), Toll-like receptor4(TLR4) and change of proinflammatory and anti-inflammatory markers in patients with acute coronary syndrome (ACS), stable angina (SA), and normal control (NC) subjects.Methods:The circulating levels of BACH2and TLR4were evaluated in peripheral blood mononuclear cells (PBMCs) and in separated lymphocytes and monocytes of35ACS,35SA and40NC subjects measured by RT-PCR and western blotting. The serum ox-LDL level and the signature cytokines of T-helperl (TH1), TH2, TH17and T-regulatory (Treg) cells i.e IFN-Y, IL-4,1L-17and TGF-01respectively were measured by ELISA method. In vitro, we evaluated the effect of silencing BACH2and blockage of TLR4on proinflammatory and anti-inflammatory markers in cultured monocytes and lymphocytes stimulated with ox-LDL. The effect of ox-LDL and the sera derived from a subgroup of ACS patients and NC subjects on expression of BACH2was also evaluated.Results:The expression level of BACH2was downregulated while TLR4upregulated significantly in PBMCs of ACS patients compared to SA patients and NC subjects. ACS patients had significantly higher levels of serum ox-LDL, IFN-γ, IL-4, IL-17and low TGF-β1. Lymphocytes were noted to have higher levels of BACH2expression compared with monocytes. In vitro silencing of BACH2caused increased expression of IFN-y, IL-4and IL-17and decreased TGF-β1cytokine. Blockage of TLR4had opposite effects to those of silencing of BACH2. Increasing doses of ox-LDL down regulated the expression of BACH2. The anti-TLR4antibody (TLR4-Ab) significantly inhibits different doses of ox-LDL induced expression of proinflammatory cytokines in cultured monocytes and lymphocytes. Incubation of monocytes and lymphocytes with sera derived from ACS patients induced a significantly lower level of BACH2expression compared with sera derived from control subjects.Conclusions:Increased serum levels of oxLDL downregulate expression of BACH2in ACS patients. Decreased expression of BACH2may promote production of proinflammatory cytokines IFN-Y, IL-4and IL17and might cause rupture of atherosclerotic plaque in acute coronary syndrome.