title: Developmental Endothelial Locus-1 (Del-1) Inhibits Oxidized Low-Density Lipoprotein Activity by Direct Binding, and Its Overexpression Attenuates Atherogenesis in Mice.
abstract: Modified low-density lipoprotein (LDL) binding to scavenger receptors has been implicated in atherosclerosis. It is hypothesized that a third molecule may affect modified LDL binding, therefore, this study focuses on the soluble endogenous protein, developmental endothelial locus-1 (Del-1), as an inhibitor of oxidized LDL (oxLDL) interactions.
  
  
  
  Del-1 preferentially bound oxLDL over native LDL in a cell-free binding assay. Del-1 also inhibited DiI-labeled oxLDL uptake by scavenger receptors irrespective of the receptor type (LOX-1, SR-AI, CD36, or SR-BI) expressed in COS-7 cells, and independent of cell type (human coronary artery endothelial cells (HCAECs) or THP-1-derived macrophages). Furthermore, Del-1 suppressed oxLDL-inducedMCP-1andICAM-1expression and endothelin-1 secretion in HCAECs. Then, male Del-1 transgenic (Del-1Tg) and wild-type mice (WT) mice were established and fed a Paigen diet for 20 weeks from the age of 24 weeks. While plasma lipid concentrations did not differ between WT and Del-1Tg mice, plasma LOX-1-ligand activity was significantly lower in Del-1Tg than in WT mice. Moreover, lipid accumulation in aortic roots was significantly less in the Del-1Tg mice, evaluated with Oil red-O. Taken together, Del-1 appears to block the activity of oxLDL pharmacologically by direct binding in vitro, and attenuates atherogenesis in vivo, although its role in physiological settings are yet to be resolved.
  
  
  
  Del-1 intercepted oxLDL before its receptor binding to reduce atherogenesis. (Circ J 2016; 80: 2541-2549).
authors: Institute for Biomedical Sciences, Shinshu University.
authors: Akemi
authors: A
authors: Kakino
authors: Yoshiko
authors: Y
authors: Fujita
authors: Atsushi
authors: A
authors: Nakano
authors: Sayaka
authors: S
authors: Horiuchi
authors: Tatsuya
authors: T
authors: Sawamura
mesh_terms: D000818:Animals; D019556:COS Cells; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules; D002522:Chlorocebus aethiops; D036341:Intercellular Signaling Peptides and Proteins; D008077:Lipoproteins, LDL / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D058226:Plaque, Atherosclerotic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding; D051116:Receptors, Scavenger / Q000235:genetics / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; C491706:Edil3 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D008077:Lipoproteins, LDL; D051116:Receptors, Scavenger; C099252:oxidized low density lipoprotein