title: Oxidized HDL induces cytotoxic effects: implications for atherogenic mechanism.
abstract: Atherosclerosis can be considered as an inflammatory disease and oxidized low-density lipoprotein (oxLDL) is a critical factor in atherogenesis. Although high-density lipoprotein (HDL) is generally an antiatherogenic lipoprotein, this property can be compromised by functional impairment mainly due to oxidative modification. As such, understanding the proatherogenic properties exerted by oxidized-HDL (oxHDL) becomes more important. This study was focused on examining the role of oxHDL as a proatherogenic agent, using oxLDL as a positive control. The comparative toxicity of oxHDL and oxLDL having same range of malondialdehyde, to monocytes was evaluated. After treatment, markers for oxidative stress, inflammation, and cytotoxicity were quantitated. The results showed that like oxLDL, oxHDL induced significant oxidative stress, cytotoxicity, and release of TNF -alpha and MMP-9 in monocytes/macrophages, but was less potent than oxLDL in promoting these proatherogenic effects. Further, the effects of oxHDL for the enhanced formation of MMP-9 were found to be mediated by NADPH oxidase/ROS-JNK/ERK pathway, as one mechanism.
authors.affiliation: Research scholar Department of Biochemistry, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram 11, Kerala, India.
authors.forename: Valliyil Sasidharan
authors.initials: VS
authors.lastname: Soumyarani
authors.forename: Narayani
authors.initials: N
authors.lastname: Jayakumari
mesh_terms: D050197:Atherosclerosis / Q000209:etiology*; D002478:Cells, Cultured; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000737:chemistry / Q000633:toxicity*; D008077:Lipoproteins, LDL / Q000633:toxicity; D008315:Malondialdehyde / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018836:Inflammation Mediators; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; C099252:oxidized low density lipoprotein; D008315:Malondialdehyde; D020780:Matrix Metalloproteinase 9
keywords: Cytotoxicity; MMP-9; NADPH-oxidase; Oxidized-HDL; Oxidized-LDL; ROS