The role of low-density lipoprotein modification by mpo-derived oxidants in atherosclerosis
Year: 2014
Type: dissertation
Abstract: THE ROLE OF LOW-DENSITY LIPOPROTEIN MODIFICATION BY MPO-DERIVED OXIDANTS IN ATHEROSCLEROSIS Myeloperoxidase (MPO) is a peroxidase generated by leukocytes at sites of inflammation. Excessive production of MPO-derived oxidants is linked to the onset of inflammatory diseases. Atherosclerosis is characterised by the build up of lipid laden macrophages (foam cells) within large arteries. Oxidative modification of low-density lipoprotein (LDL) is reported to be a possible pathway that contributes to this mechanism. Although studies have defined different sources of LDL oxidation that occur in vivo, the effect of the MPO oxidant, hypothiocyanous acid (HOSCN) on LDL modification has not been comprehensively assessed. In this study, the contribution of HOSCN to LDL modification was comprehensively assessed and compared to that observed with hypochlorous acid (HOCl) and cyanate (OCN-). HOCl and HOSCN were shown to modify both the protein and lipid component of LDL, with HOSCN contributing to significant lipid peroxidation, while HOCl mainly led to apoB100 modification. OCN- exposure resulted to protein carbamylation, which is the outcome of Lys modification. The contribution of HOSCN, HOCl and OCN--modified LDL to macrophage dysfunction was also studied. In this case, increased uptake of lipids were detected when modified LDL were exposed to macrophages, though the effects of HOSCN- and OCN--modified LDL were not as significant as HOCl-modified LDL. Furthermore, the reduction in lysosomal enzyme activity was also detected after exposure of macrophages to modified LDL. The outcomes observed in this study contribute to the knowledge regarding the role of MPO and SCN-‘–derived oxidants in the development of atherosclerosis. Although MPO is an independent risk factor and a prognostic predictor of cardiovascular events, the data found in the present study is consistent with SCN- having a protective effect, which resulted in preventing foam cell formation and modulating the extent of LDL modification induced by MPO.
Author: Fahd Ismael
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Funder: Heart Research Institute
OpenAlex ID: W101855921