Particulate Matter Promotes In Vitro Receptor‐Recognizable Low‐Density Lipoprotein Oxidation and Dysfunction of Lipid Receptors

Abstract

Particulate matter may promote cardiovascular disease, possibly as a consequence of its oxidative potential. Studies using susceptible animals indicate that particulate matter aggravates atherosclerosis by increasing lipid/macrophage content in plaques. Macrophage lipid uptake requires oxidized low-density lipoprotein and scavenger receptors; same receptors are involved in particulate matter uptake. We studied in vitro particulate matter potential to oxidize low-density lipoproteins and subsequent cell uptake through scavenger receptors. Particulate matter-induced low-density lipoproteins oxidation was evaluated by the thiobarbituric acid assay. Binding/internalization was tested in wild type and scavenger receptor–transfected Chinese hamster ovary cells, and in RAW264.7 cells using fluorescently labeled low-density lipoproteins. Dose-dependent binding/internalization only occurred in scavenger receptor–transfected Chinese hamster ovary cells and RAW264.7 cells. Competition binding/internalization using particles showed that particulate matter induced decreased binding (~50%) and internalization (~70%) of particle-oxidized low-density lipoproteins and native low-density lipoproteins. Results indicate that particulate matter was capable of oxidizing low-density lipoproteins, favoring macrophage internalization, and also altered scavenger and low-density lipoproteins receptor function.

Association of chemical constituents and pollution sources of ambient fine particulate air pollution and biomarkers of oxidative stress associated with atherosclerosis: A panel study among young adults in Beijing, China

“…These studies generally found positive associations between air pollution exposure and higher levels of Ox-LDL, which are supported by the biological evidence that airborne particles promotes in intro oxidation of LDL (Manzano-Leon et al, 2013) and in vivo early atherosclerosis and systemic oxidative stress (Araujo et al, 2008). However, specific chemical constituents behind the increased oxidative stress associated with air pollution exposure are unknown.…”

“…Toxicological studies have revealed several possible biological mechanisms through which airborne particles may affect the cardiovascular system (Sun et al, 2010). In particular, increased oxidative stress following activation of the reactive oxygen system has been proposed as one of the effective mechanisms (Araujo et al, 2008;Manzano-Leon et al, 2013). Oxidized low-density lipoprotein (Ox-LDL) is a well-established biomarker for oxidative stress and atherosclerosis (Wallenfeldt et al, 2004;Itabe, 2012).…”

A Novel β-adaptin/c-Myc Complex Formation Modulated by Oxidative Stress in the Control of the Cell Cycle in Macrophages and its Implication in Atherogenesis

“…Oxidation was terminated with the addition of EDTA, and the resulting oxidized LDLs (oxLDLs) were dialysed against 150 mM NaCl containing 100 μM EDTA and then stored at 4 °C. Labeling of LDL with 1,1′-dioctadecyl-3,3,3′3′-tetramethylindocarbocyanine-perchlorate (DiI) (Molecular Probes) was performed as previously described 35 , 36 . Isolation of the HDL fraction from human plasma (density 1.063–1.21 gKBr/ml) was performed according to established methods and based on a protocol described by Toledo-Ibelles et al .…”

“…Lipid peroxidation was estimated by the thiobarbiturate assay for thiobarbituric acid reactive substances (TBARS) based on the method originally described by Wilbur et al . 38 and modified by us following a technique employed by Kovachich and Mishra 35 , 39 . Macrophages proliferating for 36 h were incubated for 12 h with LPS concentrations.…”

Early Transcriptomic Response to LDL and oxLDL in Human Vascular Smooth Muscle Cells

“…The intravascular transport of these lipoproteins is a dynamic process based on conformational changes of proteins and temporary interactions within the surface of lipoproteins, both sensitive to oxidative stress[ 16 , 17 ]. Lipoprotein oxidation due to exposure to reactive oxygen species (ROS) [ 18 , 19 ]promotes the production of foam cells and therefore phagocytosis[ 20 , 21 ]. Oxidized LDL (oxLDL), their lipoperoxides and free radicals are moved towards the cytoplasm, propagating more ROS inside the cell and perpetuating a chronic effect[ 22 ].…”