Ischemic limbs have natural compensation, the vascular system can self-remodeling by increasing oxygen supply for muscles, presented with collateral circulation formation, angiogenic growth factors and their receptors increasing at ischemic regions. The blood remodeling occurred when vascular system can not meet the need of metabolism, tissue activity, or peripheral arterial occlusion, which displays as collateral vessel expansion and blood capillary development. Recently studies demonstrated that all pathological changes caused by ischemia can be compensated via construction of collateral circulation and newly born of vessels.
Exercise can increase shear stress of vessel wall, accelerate VEGF-R expression, induce endothelial cell proliferation and differentiation, ultimately, promotes collateral circulation formation and microangiogenesis. In the present study, the MVD, VEGF and bFGF expressions in the ischemic tissues were obviously increased after exercise training, which demonstrated that exercise training can improve blood supply. In addition, exercise training can induce vessel adaptive change, such as increasing MVD, enhancing shear stress of blood current, and stimulating endothelial cell release various growth factors.
Microangiogenesis is a complex process, involving endothelial cell division, basilar membrane and extracellular matrix degradation and endothelial cell migration. Microangiogenesis is mainly characterized by the protrusion and outgrowth of capillary buds and sprouts from pre-existing blood vessels, which depends on VEGF stimulation. VEGF is a highly specific mitogen for vascular endothelial cells, which not only promotes endothelial cell division, proliferation, migration, and chemotaxis, but also facilitates mononuclear macrophage migration, accordingly, secretes various vascular growth factors, thus, indirectly accelerates microangiogenesis[6]. bFGF directly induces microangiogenesis, which further promotes the formation and mature of vessel[7], thereby, encourages microangiogenesis at the ischemic region. VEGF mobilizes bone marrow-derived EPCs proliferation and localizes in acute ischemic events, in situ differentiates into mature endothelial cell, and forms new vessels[8]. Studies confirmed that exercise effectively mobilizes marrow-derived EPC, which secretes VEGF that can promote microangiogenesis[9]. In the present study, the number of EPC of the exercise training group was greater than that of other groups, and the capability of microangiogenesis was better, which demonstrated that exercise training contributes to EPC differentiation, which may result from stimulation of exercise training on intra-cellular signal pathway or inhibition of microangiogenesis at the ischemic limbs.
Exercise training can ameliorate blood supply of ischemic lower limb, increase pain-free walking distance and maximum walking distance, thus, improve life quality. Currently, it has aroused increasing interests for the treatment of ischemic lower limbs, especially for arterial occlusive disease below knee joint. Studies have found that blood flow increased after cerebral ischemia, induced extensive expression of VEGF, and exercise training can promote collateral circulation and enlarge blood flow after cerebral ischemia. For this reason, theoretically, it is possible to induce VEGF expression using exercise training[10-13]. Here, VEGF concentration was not reach a peak at 28 days in the exercise training group, but combined with the bFGF and MVD, all these three factors were greater than those of the model and sham-surgery groups, this finding demonstrated that lower limb ischemia accelerates microangiogenesis. In addition, the differences between the exercise training and model groups showed that exercise training can enhance microangiogenesis. However, the experimental samples were small, and the observation only performed for 28 postoperative days, thus, the variation of VEGF required further investigation.
The experimental results demonstrated that, athletic sports, especially running, can promote microangiogenesis. This is benefit for explaining effects of sports on encourage microangiogenesis and enriching theoretical research of “remedial microangiogenesis” and rehabilitative treatment. Exercise training can amendment body microcirculation, mitigate inflammatory lesions, as well as enhance cardiorespiratory function, which can play its role in the treatment of chronic occlusive arterial disease.
