TITLE:
Atherogenesis, the oxidative LDL modification hypothesis revisited
AUTHORS:
Dov Lichtenberg, Ilya Pinchuk
KEYWORDS:
ROS; Free Radicals; Atherosclerosis; Oxidative Stress; Antioxidants
JOURNAL NAME:
Advances in Bioscience and Biotechnology,
Vol.4 No.11A,
December
27,
2013
ABSTRACT:
The commonly-accepted “oxidized LDL hypothesis of atherogenesis” is based on a large number of indirect evidence that shows that
oxidatively-modified LDL plays a role in atherogenesis. Yet, the exact
role is not clear. Some researchers think that oxidatively modified
biomolecules initiate atherogenesis; others believe that they “only” promote
this multifactorial process. Regardless of the exact mechanism responsible
for the effect of peroxidation on atherogenesis, the “oxidative theory of AS”
is apparently inconsistent with the results of meta-analysis, in which (the “expected”) significant correlation between CVD and oxidative stress (OS) was
found only when the OS was evaluated on the
basis of the plasma concentrations of malondialdehyde (MDA), often based
on the concentration of thiobarbituric acid reactive substances (TBARS).
Notably, even this association is questionable due to 1) poor reliability of
the laboratory assay of MDA and 2) possible publication bias. Hence, it appears
that the commonly accepted paradigm regarding the role of oxidative damage in
the pathogenesis of CVD has been overestimated. Furthermore, the hypothesis
is apparently inconsistent with the disappointing results of most of the
clinical trials that were designed to reduce OS by means of supplementation
of antioxidants, mostly vitamin E. These apparent inconsistencies do not
contradict the oxidative modification hypothesis of AS. The source of the apparent
contradictions is probably the oversimplified considerations on which the
predictions have been based. Many reasonable arguments can be raised to explain the apparent contradictions, which means that
our current knowledge is insufficient to test the relationship of oxidative
stress to cardiovascular disease.