Background: Cardiovascular diseases account for the highest mortality rate in the United States. The
major underlying mechanism driving the onset and maintenance of cardiovascular diseases is atherosclerosis.
Atherosclerosis is a chronic disease affecting large and medium-size arteries; it proceeds through four main stages
along different decades of life, beginning at birth. Atherosclerosis is a consequence of oxidative stress, where
homeostasis between endogenous antioxidants and reactive oxygen species is disrupted. Failure of intrinsic antioxidants
and prophylactic antioxidant supplements to prevent atherosclerosis formation is an ongoing area of
research in the race to avert, manage and cure atherosclerosis.
Methods: The purpose of this work was to elucidate the actions of reactive oxygen species and oxidative stress on
the formation of atherosclerosis as well as the different stages of atherosclerosis and the different mechanisms to
prevent it. Through an extensive review of scientific literature, this paper correlates cell damage caused by oxidative
stress to atheromatous plaque formation, as well as an in-depth analysis of high-density lipoproteins and
enzymatic and non-enzymatic antioxidant role on atherosclerosis prevention. The antioxidant mechanism is
overwhelmed by atherosclerotic processes and fails to be the ideal treatment of atherosclerosis. There is no scientific
data that correlates prophylactic and non-prophylactic antioxidant treatment to a decrease in mortality or
comorbidities pertaining to atherosclerosis. This is thought to be due to lack of consensus of optimal therapeutic
doses, lack of reliable markers indicating which patient is to benefit from therapy and the chemical complexity of
antioxidants in vivo. Current treatments for atherosclerosis include HMG-CoA reductase inhibitors which directly
target low-density lipoproteins to tackle atherosclerotic plaque formation.
Conclusion: HMG-CoA reductase inhibitors are not enough for the treatment of atherosclerosis given the complexity
of the disease which has immune, musculoskeletal, genetic and hematologic aspects besides the involvement
of lipids and lipoproteins. Therefore, other pharmacologic targets such as the PCSK9 enzyme and NFK- β
should be researched in depth as possible treatments for atherosclerosis.