title: How do macrophages sense modified low-density lipoproteins?
abstract: In atherosclerosis, serum lipoproteins undergo various chemical modifications that impair their normal function. Modification of low density lipoprotein (LDL) such as oxidation, glycation, carbamylation, glucooxidation, etc. makes LDL particles more proatherogenic. Macrophages are responsible for clearance of modified LDL to prevent cytotoxicity, tissue injury, inflammation, and metabolic disturbances. They develop an advanced sensing arsenal composed of various pattern recognition receptors (PRRs) capable of recognizing and binding foreign or altered-self targets for further inactivation and degradation. Modified LDL can be sensed and taken up by macrophages with a battery of scavenger receptors (SRs), of which SR-A1, CD36, and LOX1 play a major role. However, in atherosclerosis, lipid balance is deregulated that induces inability of macrophages to completely recycle modified LDL and leads to lipid deposition and transformation of macrophages to foam cells. SRs also mediate various pathogenic effects of modified LDL on macrophages through activation of the intracellular signaling network. Other PRRs such Toll-like receptors can also interact with modified LDL and mediate their effects independently or in cooperation with SRs.
authors.affiliation: Department of Molecular Genetic Diagnostics and Cell Biology, Division of Laboratory Medicine, Institute of Pediatrics, Research Center for Children's Health, 119991 Moscow, Russia.
authors.forename: Dimitry A
authors.initials: DA
authors.lastname: Chistiakov
authors.affiliation: Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, Moscow 125315, Russia.
authors.forename: Alexandra A
authors.initials: AA
authors.lastname: Melnichenko
authors.affiliation: Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, Moscow 125315, Russia; Institute for Atherosclerosis Research, Skolkovo Innovative Center, Moscow 121609, Russia.
authors.forename: Alexander N
authors.initials: AN
authors.lastname: Orekhov
authors.affiliation: Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, Moscow 125315, Russia; Institute for Atherosclerosis Research, Skolkovo Innovative Center, Moscow 121609, Russia; Faculty of Medicine, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia; School of Medicine, University of Western Sydney, Campbelltown, NSW 2560, Australia. Electronic address: y.bobryshev@mail.ru.
authors.forename: Yuri V
authors.initials: YV
authors.lastname: Bobryshev
mesh_terms: D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology; D005487:Foam Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D051116:Receptors, Scavenger / Q000378:metabolism
chemical_list: D008077:Lipoproteins, LDL; D051116:Receptors, Scavenger
keywords: Atherosclerosis; Foam cell formation; Macrophage; Modified LDL; Scavenger receptor; Toll-like receptor