Dual signaling evoked by oxidized LDLs in vascular cells

Article ID	Journal	Published Year	Pages	File Type
5501762	Free Radical Biology and Medicine	2017	42 Pages	PDF

Abstract

Oxidized LDLs (oxLDLs) exerts a dual signaling on vascular cells, depending on their heterogeneity, their local concentration and their uptake by scavenger receptors (SRs). Low oxLDLs concentrations stimulate the production of ROS and low carbonyl stress, and trigger cell signaling responses (activation of receptor tyrosine kinase and the sphingolipid pathway), involved in inflammation, cell proliferation, survival or angiogenesis. High concentrations of oxLDLs generate oxidative stress and high carbonyl stress that inhibit angiogenesis and tyrosine kinase receptors, trigger endoplasmic reticulum stress (ER stress) activation and cytosolic calcium deregulation, generate an imbalance of the sphingolipid pathway, and finally lead to apoptosis.267

Keywords

ECM PDI NF-κB MMP EGF LPS CCL2 IGF Jnk 4-HNE 4-hydroxynonenal NFAT LRP HDL Nrf2 AAPH GSH GPX HO-1 ICAM-1 FGF CDE LDLR PPARγ MUFA LPC SRS IκB MPTP AP-1 HIF-1α UPR IRE1 S1P ATF6 IKK GM-CSF SMase MCP1 LPPS PDGF TLR4 S1PR CHD MT1-MMP SMCs LXR heme-oxygenase-1 IDL LOX-1 4-HHE lectin-like oxidized LDL receptor-1 RCCs LDLs MDA AMVN PCNA 2,2'-Azobis(2-amidinopropane) dihydrochloride OxPLs IAP-1 inositol-requiring kinase 1 4-Hydroxyhexenal c-Jun N-terminal kinase IκB kinase JAK/STAT Mn-SOD NOx ROS RTKs Hydrogen peroxide Proliferating Cell Nuclear Antigen AIF sphingomyelin Sphingosine kinase Sphingosine-1-phosphate sphingomyelinase Polyunsaturated fatty acid monounsaturated fatty acid PUFA mitochondrial permeability transition pore Clathrin-dependent endocytosis NADPH oxidase coronary heart disease Terminal deoxynucleotidyl transferase dUTP nick end labeling Reactive carbonyl compounds tumor necrosis factor-α TUNEL RTK, Receptor tyrosine kinase Cer ceramide Smooth muscle cells endothelial nitric oxide synthase manganese-dependent superoxide dismutase endoplasmic reticulum hypoxia inducible factor 1α Granulocyte macrophage colony stimulating factor epidermal growth factor Transcription factor nuclear factor of activated T-cells Vascular endothelial growth factor Vascular Endothelial Growth Factor (VEGF)Insulin growth factor platelet derived growth factor fibroblast growth factor Platelet-activating factor TNF-α nuclear factor (erythroid-derived 2)-like 2 nuclear factor kappa-light-chain-enhancer of activated B cells Phosphatidylserine oxidized phospholipids activating transcription factor 6 Lysophosphatidylcholine high density lipoprotein low density lipoproteins Intermediate density lipoprotein lipopolysaccharide Extracellular matrix malondialdehyde Metalloprotease Lipid peroxidation products inhibitor of NF-κB intercellular adhesion molecule MicroRNA Nitric oxide PAF H2O2 Familial hypercholesterolemia e-NOS Unfolded protein response protein disulfide isomerase activator protein 1 LDL receptor-related protein protein kinase RNA-like endoplasmic reticulum kinase PERK liver X receptor Glutathione glutathione peroxidase Reactive oxygen species LDL receptor S1P receptor Toll-like receptor-4 Scavenger receptors peroxisome proliferator-activated receptor γ