title: Elastin aging and lipid oxidation products in human aorta.
abstract: Vascular aging is associated with structural and functional modifications of the arteries, and by an increase in arterial wall thickening in the intima and the media, mainly resulting from structural modifications of the extracellular matrix (ECM) components. Among the factors known to accumulate with aging, advanced lipid peroxidation end products (ALEs) are a hallmark of oxidative stress-associated diseases such as atherosclerosis. Aldehydes generated from the peroxidation of polyunsaturated fatty acids (PUFA), (4-hydroxynonenal, malondialdehyde, acrolein), form adducts on cellular proteins, leading to a progressive protein dysfunction with consequences in the pathophysiology of vascular aging. The contribution of these aldehydes to ECM modification is not known. This study was carried out to investigate whether aldehyde-adducts are detected in the intima and media in human aorta, whether their level is increased in vascular aging, and whether elastin fibers are a target of aldehyde-adduct formation. Immunohistological and confocal immunofluorescence studies indicate that 4-HNE-histidine-adducts accumulate in an age-related manner in the intima, media and adventitia layers of human aortas, and are mainly expressed in smooth muscle cells. In contrast, even if the structure of elastin fiber is strongly altered in the aged vessels, our results show that elastin is not or very poorly modified by 4-HNE. These data indicate a complex role for lipid peroxidation and in particular for 4-HNE in elastin homeostasis, in the vascular wall remodeling during aging and atherosclerosis development.
authors.affiliation: Division of Pathology, Clinical Hospital Centre, Zagreb, Croatia.
authors.forename: Kamelija
authors.initials: K
authors.lastname: Zarkovic
authors.affiliation: Inserm UMR-1048, Toulouse, France; University of Toulouse, Toulouse, France.
authors.forename: Pauline
authors.initials: P
authors.lastname: Larroque-Cardoso
authors.affiliation: Inserm UMR-1048, Toulouse, France; University of Toulouse, Toulouse, France.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Pucelle
authors.affiliation: Inserm UMR-1048, Toulouse, France; University of Toulouse, Toulouse, France.
authors.forename: Robert
authors.initials: R
authors.lastname: Salvayre
authors.affiliation: Institute of Molecular Biosciences, University of Graz, Austria.
authors.forename: Georg
authors.initials: G
authors.lastname: Waeg
authors.affiliation: Inserm UMR-1048, Toulouse, France; University of Toulouse, Toulouse, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Nègre-Salvayre
authors.affiliation: Rudjer Boskovic Institute, LabOs, Zagreb, Croatia; University for Applied Sciences Baltazar, Zaprešić, Croatia. Electronic address: zarkovic@irb.hr.
authors.forename: Neven
authors.initials: N
authors.lastname: Zarkovic
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000447:Aldehydes / Q000378:metabolism; D001011:Aorta / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology; D001344:Autopsy; D004549:Elastin / Q000378:metabolism* / Q000648:ultrastructure; D005109:Extracellular Matrix / Q000378:metabolism / Q000648:ultrastructure; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D005260:Female; D006801:Humans; D015227:Lipid Peroxidation; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D018384:Oxidative Stress
chemical_list: D000447:Aldehydes; D005231:Fatty Acids, Unsaturated; D004549:Elastin; C027576:4-hydroxy-2-nonenal
keywords: 4-hydroxynonenal; Aging; Atherosclerosis; Elastin; Extracellular matrix; Smooth muscle cells