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[ 16 ]. These factors are able to recruit inflammatory cells to the vessel wall, which in
turn can induce cascade expression of inflammatory factors, such as MCP-1, and
cytokines including interferon Gamma (IFN-y), tumor necrosis factor-α (TNF-α)
and interleukin-6 (IL-6) [ 17 , 18 ]. Later on, smooth muscle cells (SMC) migrate
from the tunica media into the intimal or sub-endothelial space and participate in the
reaction. Finally, a fibrous cap would be built [ 19 ].
Recent studies demonstrated that physical inactivity can lead to the accumula-tion of visceral fat and consequently result in the activation of oxidative stress and
inflammation cascade, which eventually enhances the progression of atherosclero-
sis [ 20 ]. Regular physical exercise confers plentiful effects in restraining the athero-
genic process, which involved arterial wall remodeling, plaque size modulation,
macrophage function regulation and inflammatory reaction control [ 21 ]. In animal
study, regular physical exercise corrects cardiovascular and metabolic risk factors to
baseline level in obese rats that were fed on a high-fat diet [ 22 ]. On the other hand,
exercise can prevent the conversion of plaques into a vulnerable phenotype [ 23 ],
which is the main trigger of acute coronary syndrome. Randomized clinical trials
have validated the role of physical exercise in primary and secondary prevention of
atherosclerosis, CVD, and decrease mortality among adults [ 24 , 25 ].
2.1 Physical Exercise Reduces Atherosclerosis Process
Physical exercise prevents atherosclerotic plaque development and induces the
regression of coronary stenosis possibly by preventing and reducing inflammatory
reaction, oxidative stress and regulating endothelial function. Besides, physical
exercise can normalize blood pressure, insulin resistance, serum lipid level [ 15 ],
which all are crucial factors during atherosclerosis development.
2.2 Physical Exercise Exerts Anti-inflammatory Effects
Chronic inflammation is one of the most important features of atherosclerosis and
persists throughout the whole process. It starts with the release of pro-inflammatory
factors including cytokines and nuclear factor-κB (NF-κB). NF-κB, a pro-
inflammatory transcription factor, can upregulate the transcription of other pro-
inflammatory molecules, such as tumor necrosis factor-α (TNF-α), interleukins
(IL-1β, and IL-6), cyclo-oxygenase-2 (COX-2), and nitric oxide synthase (iNOS).
Apart from this, it is also associated with oxidative stress production and disease
related to aging [ 26 – 28 ]. One study showed that combination of exercise and Korean
red ginseng supplement or exercise alone could decrease serum CRP, NF-kB, TNF-
α, COX-2, IL-6, ICAM-1 and VCAM-1 in aorta of D-gal induced aging atheroscle-
rotic rats [ 29 ]. Another report showed that higher intensity exercise enhanced
NF-κB activation, which consequently bring adverse effect to CVD [ 30 , 31 ].
15 Physical Exercise Is a Potential “Medicine” for Atherosclerosis