Elastin peptides induced oxidation of LDL by phagocytic cells.
The degradation products of one of the major component of vascular wall, elastin, have several important biological activities. Elastin peptides (KE) are mostly generated during vascular aging and the atherosclerotic process. They induce free radical and proteases production from cells, which are the major components of the atherosclerotic process. In the present study, we investigated whether the interaction between elastin peptides and neutrophils as well as monocytes contributes to low density lipoproteins (LDL) oxidation, being one of the most important initiator of the chronic inflammatory process contributing to the development of atherosclerosis. Here, we present data on the link between the elastin degradation products and LDL oxidation by the chemotactically attracted neutrophils and monocytes. The KE as well as the active epitope, the hexapeptide VGVAPG is able, in a differential concentration and time dependence, to induce the oxidation of LDL. KE is able to induce via the production of free radicals by neutrophils the oxidation of LDL very rapidly and in higher concentration compared to monocytes. These effects of KE are occurring through the stimulation of the 67 kDa elastin-laminin receptor (ELR), as demonstrated by the uncoupling effect of lactose. In our present study, the HDL was able to decrease the LDL oxidation by KE. This is a new mechanism by which elastin peptides might participate in the initiation and progression of the atherosclerotic process.
Fulop
Tamas
T
Centre de Recherche sur le vieillissement, Faculté de Médecine, Université de Sherbrooke, Que., Canada. tamas.fulop@usherbrooke.ca
Larbi
Anis
A
Fortun
Axelle
A
Robert
Ladislas
L
Khalil
Abdelouahed
A
D000375:Aging / Q000502:physiology; D004549:Elastin / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008077:Lipoproteins, LDL / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D010586:Phagocytes / Q000187:drug effects / Q000378:metabolism*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014810:Vitamin E / Q000378:metabolism
D008077:Lipoproteins, LDL; D010446:Peptide Fragments; D017392:Thiobarbituric Acid Reactive Substances; C099252:oxidized low density lipoprotein; D014810:Vitamin E; D009240:N-Formylmethionine Leucyl-Phenylalanine; D004549:Elastin