World Cardiology Meeting

Biography

Biography: Mizanur Rahman

Abstract

In atherosclerotic plaques, immune cells especially dendritic cells (DCs), T-cells and M1 macrophages are abundant. These cells when activated could play an important role in plaque rupture and thus, cardiovascular disease (CVD). T-cells in atherosclerotic plaques can be activated in response to oxidized low density lipoprotein (OxLDL) but role of different components including malondialdehyde (MDA) in OxLDL is not clear, though MDA, which forms adduct with proteins, is implicated. Here, we study MDA conjugated with human serum albumin (MDA-HSA). DCs, differentiated from human monocytes were stimulated with MDA-HSA and co-cultured with autologous T-cells from human blood or atherosclerotic plaques or T cells were stimulated directly with MDA-HSA. In addition, monocytes or macrophages were also stimulated with MDA-HSA. MDA-HSA-stimulated-DC induced activation of pro-inflammatory T-cell as determined by FAC Scan, intracellular or extracellular cytokine as well as transcription factors. Direct effect of MDA-HSA on T cells was pronounced. The DCs mediated but not the direct activation was T-cell receptor dependent. MDA-HSA induced expression of TLR2 & TLR4, and induced activation of inflammatory pathway mitogen-activated protein kinase. Either anti-MDA antibodies or an inhibitor of mitochondrial reactive oxygen species (ROS) affected MDA-HSA induced activation of T-cells. MDA modified peptide sequences of HSA in vitro were similar to MDA modified peptide sequences was observed in atherosclerotic patients’ plasma. Monocyte or macrophages differentiated into pathogenic macrophages in response to MDAHSA. MDA-HSA could play a role in promoting plaque rupture. Anti-MDA antibodies or ROS inhibitor could be potential candidate to reduce plaques inflammation and thus, instability.