Exercise for Cardiovascular Disease Prevention and Treatment From Molecular to Clinical, Part 1

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will start to express cell adhesion molecules (CAMs), such as ICAM-1, VCAM-1,

E-selectin, and P-selectin. They are all essential to the recruitment of inflammatory

cells [ 120 ]. While physical exercise has a positive effect in the circulating CAMs.

Circulating ICAM-1, VCAM-1, and P-selectin are found to be significantly

decreased after 2 weeks of exercise training [ 121 – 123 ]. Similarly, physical exercise

performed 5 times per week for 6–8 weeks decreases circulating P-selectin andV-

CAM- 1 levels [ 124 ]. Shear stress induced during physical exercise could probably

contribute to these effects [ 125 ]. Besides, apart from the direct impact on CAMs

expression, physical exercise might also have indirect beneficial effects throughout

the reduction of agonists of CAM synthesis [ 43 , 126 , 127 ].

Endothelin-1 (ET-1), which is expressed by vascular endothelial cells, has strong

constrictor and proliferative activity on SMCs. Because of this, it has been implicated

in modulation of vascular contraction and progression of atherosclerosis. Its produc-

tion has been found to be elevated in human atherosclerotic lesions [ 128 – 130 ]. It was

found that in healthy adults, physical exercise is able to suppress its level [ 131 , 132 ].

In all, by reducing the soluble adhesion molecules which may represent the inter-

action between activated monocytes/macrophages and endothelial cells and ET-1

concentration, physical exercise might be considered as an effective non-

pharmacological intervention to reduce endothelial adhesiveness.

2.5 Physical Exercise Regulates Macrophages Function

Macrophage has been studied for centuries for its role in inflammatory response. In

addition to modulating immune reaction, it is also noticed to take great part in the

atherosclerotic process. Macrophage is able to modulate lipid metabolism. During

the early phase of plaque formation, macrophages become foam cells when it can

not process OxLDL. Foam cells are the hallmarks of atherosclerotic lesions and

vulnerability [ 133 , 134 ]. Macrophages have been parsed into at least two

subtypes(M1 and M2), each of which have specific roles in atherosclerosis [ 135 –

138 ]. M1 macrophages produce high levels of pro-inflammatory factors like CD40,

CD80, IL-6, TNF-α, iNOS [ 139 ]. While M2 macrophages leads to more foam cell

formation with higher phagocytic nature and greater ability to import OxLDL. Foam

cell–prone M2 macrophages level is higher than pro-inflammatory M1 macrophages

in the early atherosclerotic lesions; but the ratio reverses as the lesion progresses

[ 140 ]. In addition, macrophages express MMPs to stable plaques during atherogen-

esis [ 141 – 143 ]. Additionally, HHcy may be a primary cause for the macrophages

dysfunction that leads to the effect on atherosclerosis [ 142 , 144 ].

Physical exercise prevents foam cell formation. It accelerates the transportation

of cholesterol from macrophages to the liver which has been considered as the ini-

tial step of atherosclerosis [ 145 ]. Moreover, physical exercise encourages accumu-

lation of collagen and elastin by modulating serum level of MMPs and TIMP-1.

This greatly keep the plaque stability and reduce in lesion incidence and arterial

stenosis [ 146 – 148 ].

15 Physical Exercise Is a Potential “Medicine” for Atherosclerosis