NO - Besoin d'assistance

Mechanisms and Biomarkers (WG 4) page 54
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1993; Neuzil et al.,1997; Ingold et al., 1993; Witting et al., 1995; Witting et al., 1997).
Consequently the characteristic of lipid peroxidation cannot be explained by the conventional
antioxidant action of α-tocopherol (chain-breaking antioxidant). These discrepancies may be
explained by the tocopherol-mediated peroxidation (TMP) model (Bowry and Stocker, 1993)
which has been recently deeply explored and discussed (Upston et al., 1999). TMP is a
general model for radical-induced lipoprotein oxidation and its prevention by coantioxidants;
this could explain why vitamin E together with coantioxidants may be superior in protecting
lipoproteins from oxidation (Upston et al., 1999). It should also be noted that α-tocopherol has
additional metabolic roles, such as the regulation of smooth muscle cell proliferation (Azzi et
al., 1999) which may complicate any assessment of its antioxidant function. The nonantioxidant
effects of Vitamin E take place at the level of cell signalling and gene expression.
Data suggest the existence of a ligand/receptor type of mechanism, where oxidant stress
causes a loss of antioxidant molecules such as vitamin E, which at 10-50µM specifically
increases protein phosphatase 2A1 activity. This activation is followed by PKCα
dephosphorylation and by a decrease in PKC activity. This vitamin E downregulation of PKC
activity modulates the expression of collaginase MMP-I and α-Tropomyosin. This same
mechanism has also been demonstrated to prevent cell adhesion, to inhibit platelet
aggregation, to prevent smooth muscle cell proliferation and to inhibit the PKC dependent
oxygen burst (Azzi et al., 1999).
β-carotene - The "oxidative hypothesis of atherosclerosis" raises the possibility that also β-
carotene may prevent or delay the progression of atherosclerosis. To support this hypothesis
several observational, prospective cohort studies showing a risk reduction associated with the
ingestion of foods rich in β-carotene have been advocated. However, the effects of β-carotene
on LDL oxidation are not so evident. Supplementation of humans with β-carotene does not
result in increased resistance of plasma-derived LDL to ex vivo oxidation (Reaven et al.,
1993; Princen et al., 1992; Gaziano et al., 1995; Reaven et al., 1994). As in all these studies
LDL was incubated under ambient pO2 (approximately 150 mm hg), while it is known that β-
carotene acts as an efficient antioxidant only at low physiological pO2, Reaven et al. (1994)
addressed this question by incubating LDL from β-carotene supplemented subjects with Cu 2+
at the lower oxygen tensions typically present in the artery wall (35 mm hg and 15 mm hg);
no increased resistance to oxidation of β-carotene-enriched LDL compared to control LDL
was observed under all incubation conditions. Similar results were obtained in vitro by Hatta