title: Proatherogenic effects of 4-hydroxynonenal.
abstract: 4-hydroxy-2-nonenal (HNE) is a α,β-unsaturated hydroxyalkenal generated by peroxidation of n-6 polyunsaturated fatty acid. This reactive carbonyl compound exhibits a huge number of biological properties that result mainly from the formation of HNE-adducts on free amino groups and thiol groups in proteins. In the vascular system, HNE adduct accumulation progressively leads to cellular dysfunction and tissue damages that are involved in the progression of atherosclerosis and related diseases. HNE contributes to the atherogenicity of oxidized LDL, by forming HNE-apoB adducts that deviate the LDL metabolism to the scavenger receptor pathway of macrophagic cells, and lead to the formation of foam cells. HNE activates transcription factors (Nrf2, NF-kappaB) that (dys)regulate various cellular responses ranging from hormetic and survival signaling at very low concentrations, to inflammatory and apoptotic effects at higher concentrations. Among a variety of cellular targets, HNE can modify signaling proteins involved in atherosclerotic plaque remodeling, particularly growth factor receptors (PDGFR, EGFR), cell cycle proteins, mitochondrial and endoplasmic reticulum components or extracellular matrix proteins, which progressively alters smooth muscle cell proliferation, angiogenesis and induces apoptosis. HNE adducts accumulate in the lipidic necrotic core of advanced atherosclerotic lesions, and may locally contribute to macrophage and smooth muscle cell apoptosis, which may induce plaque destabilization and rupture, thereby increasing the risk of athero-thrombotic events.
authors.affiliation: Inserm UMR-1048, France. Electronic address: anne.negre-salvayre@inserm.fr.
authors.forename: Anne
authors.initials: A
authors.lastname: Nègre-Salvayre
authors.affiliation: Inserm UMR-1048, France.
authors.forename: Sandra
authors.initials: S
authors.lastname: Garoby-Salom
authors.affiliation: Inserm UMR-1048, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Swiader
authors.affiliation: Inserm UMR-1048, France.
authors.forename: Myriam
authors.initials: M
authors.lastname: Rouahi
authors.affiliation: Inserm UMR-1048, France.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Pucelle
authors.affiliation: Inserm UMR-1048, France; University of Toulouse, Faculty of Medicine, Biochemistry Dept, Toulouse, France; CHU Toulouse, Rangueil, Toulouse, France.
authors.forename: Robert
authors.initials: R
authors.lastname: Salvayre
mesh_terms: D000447:Aldehydes / Q000378:metabolism*; D000818:Animals; D001011:Aorta / Q000378:metabolism* / Q000473:pathology; D001055:Apolipoproteins B / Q000235:genetics / Q000378:metabolism; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D015227:Lipid Peroxidation; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction
chemical_list: D000447:Aldehydes; D001055:Apolipoproteins B; D008077:Lipoproteins, LDL; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495635:NFE2L2 protein, human; C099252:oxidized low density lipoprotein; C027576:4-hydroxy-2-nonenal
keywords: Adducts; Angiogenesis; Apoptosis; ER stress; HNE; HNE-scavengers; Inflammation; Lipid peroxidation; Oxidative stress; Oxidized LDL; Proliferation; Protein adduct