Aging of the vascular wall and atherogenesis: role of the elastin-laminin receptor.
Aging of the vascular wall, arteriosclerosis and focal lipidic plaques, atheromatosis, often occur together but may occur separately as lipidic lesions in young children or vascular aging in some animal species resistant to lipid-rich diet as the rat. Most theories of athero-arteriosclerosis claim an endothelial lesion for its initiation, without proposing a detailed mechanism. The elastin-laminin receptor present also on endothelial cells, mediates NO.-dependent vasorelaxation. It could be shown that chronic exposure to higher concentrations of the agonist, elastin peptides, present in human blood at microgram/ml concentrations, and also during aging, the receptor gets "uncoupled" from its transmission pathway (G-protein, PLC, PKC) but continues releasing free radicals as superoxyde. NO. and O2-. give peroxynitrite, a toxic anion, needing GSH for its neutralisation. GSH production decreases with age. This process decreases available NO. for vasorelaxation and could then contribute to age-dependent blood pressure increase and produce the endothelial lesions leading to the development of athero-arteriosclerosis.
Robert
L
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Laboratoire de Biologie Cellulaire, Paris, France.
D000375:Aging / Q000473:pathology*; D000818:Animals; D001158:Arteries / Q000378:metabolism / Q000473:pathology*; D001161:Arteriosclerosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D005609:Free Radicals; D005978:Glutathione / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000209:etiology; D008055:Lipids / Q000097:blood; D009569:Nitric Oxide / Q000502:physiology; D051381:Rats; D011956:Receptors, Cell Surface / Q000502:physiology*; D017474:Receptors, Laminin / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology*
D005609:Free Radicals; D008055:Lipids; D011956:Receptors, Cell Surface; D017474:Receptors, Laminin; C054901:elastin-binding proteins; D009569:Nitric Oxide; D005978:Glutathione