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

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Endothelial cell integrity is crucial for preserving vascular homeostasis. It allows

the continuous adjustment of vascular tone, regulation of leukocyte traffic, and also

maintenance of blood fluidity [ 97 ]. Endothelial dysfunction refers to an injury of

endothelium-dependent vasorelaxation. Vulnerable plaques are sites of active

inflammation and oxidative stress. They are most likely to locate where there is

impaired endothelial function. Endothelial dysfunction presents in all stages of ath-

erosclerosis process. The impaired endothelial cells release lower levels of NO,

thrombomodulin, prostacyclin and tissue plasminogen activator but increase the

release of endothelin-1, angiotensin II, plasminogen activator inhibitor (PAI)-1 [ 98 ,

99 ]. However, clinical and experimental findings clearly demonstrate that physical

exercise can counteract these destructive effects [ 100 , 101 ]. Researchers found that

a primary target of the physical exercise intervention appears to be the impaired

endothelial function [ 102 , 103 ].

Inflammatory factors like NO and CRP are crucial in endothelial homeostasis.

Loss of NO bioactivity seems as an early event in the pathogenesis of atherosclero-

sis [ 69 ]. CRP is produced in response to IL-6, and its pro-atherogenic effects are

applied through damaging the endothelial function. Both of them could be down-

regulated by physical exercise.

Interestingly, researchers also found that endothelial impairment is accompanied

by increased blood pressure, insulin resistance and dyslipidemia [ 104 , 105 ]. This

suggests that the concurrent appearance of these risk factors might share a common

mechanism. Given this information, physical exercise preserves endothelial func-

tion by controlling blood pressure through regulation of AII receptor (type I) and

increasing skeletal muscle endothelial nitric oxide synthase content [ 106 , 107 ]. By

controlling one factor, physical exercise helps to decrease the risk for all other

chronic metabolic disease. Besides, another study demonstrated that acute dynamic

resistance exercise can decrease resting blood pressure and reactivity to phenyleph-

rine and increased endothelium-dependent relaxation [ 108 ].

In patients with CVD, physical exercise reverses endothelial dysfunction and

increases CBF [ 109 – 111 ]. While in patients with Type 2 diabetes and obesity, simi-

lar results have been observed [ 112 , 113 ] but without concomitant changes in tradi-

tional risk factors. All these results encourage physical exercise for both treatment

and prevention of these endothelial function-centered disease [ 114 – 117 ].

2.4 Physical Exercise Reduces Endothelial Adhesiveness

Endothelial adhesiveness plays important role in the development of atherosclero-

sis. Within a week after the initiation of a high-cholesterol diet, monocytes adher-

ence to the endothelium and starts to migrate. It leads to the development of intimal

lesions, which contain sub-endothelial macrophage-derived foam cells, small num-

bers of non-lipid-filled macrophages and T lymphocytes [ 118 , 119 ]. Under normal

physiologic conditions, endothelial cell does not secrete factors that induce the

adhesion molecules. Once activated by cytokines, oxLDL, or ROS, endothelial cells

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