Present study examined probable changes in angiogenic factors in response to eight weeks of Circuit Resistance Training and Traditional Resistance Training. The major findings were that eight weeks of either CRT or TRT increased pre to post values of GH, bFGF and VEGF, the factors that previously mentioned as positive effectors on angiogenesis.
As one of the primary determinants of angiogenesis, GH identified as a main contributor in angiogenesis process (10, 13). This content verifies by our data showing enhanced GH after training period, where both of training modalities revealed a significant increase in post-training compared to pre-training. This increase was insignificantly higher in response to CRT compared to TRT. Previous studies verified that stimulation of endothelial cells following mechanical effects of muscle contraction and increased muscle flow after physical training increase GH production (13). It is acceptable that an increased level of this hormone leads to transition, proliferation, survival and reproduction of endothelial cells (28, 29). It is highly probable that CRT and TRT activate GH-IGF1 pathway, a hormonal axis that previously verified as a major angiogenic regulator (10, 11, 13, 30). However, there are still uncertainties in determining which mechanisms directly stimulate GH secretion during physical activity.
In present report, VEGF significantly increased in response to both training modalities compared with pre-training, but not in control group. However, the magnitude of these improvements was not significantly different between training modalities indicating beneficial angiogenic effects of both protocols. It is generally accepted that increase in VEGF induce angiogenic downstream pathways in skeletal muscles and cardiac tissue (2, 3, 17).
The current findings support previous studies that have documented elevations in VEGF levels following endurance, resistance or combined training (2, 15, 16, 17, 19, 20, 21, 22, 31, 32). In contrast, Landers-Ramos et al (2014) did not report significant change in VEGF after acute aerobic training (26). This inconsistency might be as a reason of resistance-recruitment part of CRT and the nature of TRT utilized in this study. Also Krenc et al (2016) reported significant decreases in VEGF level after long-term endurance training (14). It seems that the effects of endurance training on VEGF levels may vary depending on factors such as the duration and intensity of the training program, differences between subjects of studies, and different methods used to measure VEGF levels.
Although the level of VEGF enhancement was not significantly different between TRT and CRT, it seems that the reasons that cause slightly higher increase of this factor following CRT compared to TRT are not the same. Following TRT, studies mostly reported that VEGF enhancement triggers by local hypoxia induced by overload on muscles or muscle tissue stretch, because of higher involvement of cross-sectional area of capillaries in skeletal muscles (1, 33). In addition, the accumulation of lactate and adenosine during TRT increases cAMP concentration and the subsequent increase in the VEGF levels (34). The heightened blood flow to active tissues (Cardiac tissue and skeletal muscles) due to the aerobic nature of CRT, elicits a hydrodynamic-frictional force on the vascular wall, which refers to as shear stress. This phenomenon triggers VEGF gene expression and subsequently, results in vasodilation (6, 8).
The other important finding was pre to post-training increases in bFGF levels in both training modalities. Few studies reported controversial role of bFGF in angiogenesis following physical training. Our findings support previous reports stating elevated BFGF in response to resistance training (16, 35); and aerobic training (14, 15, 26, 35) which is known as a training regimen which is partly similar to CRT (26), while Wahl et al (2011) reported no significant changes in BFGF in response to both of high and low intensity exercise trainings (36). The observed contradiction may have arisen due to the disparate characteristics of the employed training protocols. As mentioned, both of utilized training modalities are similar in resistance-recruitment part, while CRT involves partly in aerobic characteristics of training (2, 22, 24). We speculate that bFGF enhancement induces in response to mechanical stress on muscles during overload engagement in resistance exercise.
In reviewing scientific documents about angiogenesis overally, there is now a considerable body of evidence linking beneficial adaptation of angiogenesis and capillary formation after Aerobic, resistance and circuit training (17, 31, 35, 37). However, several studies reported contradictory findings. For instance, Tesch et al (1984) suggested that heavy resistance training can stimulate angiogenesis, which may contribute to the increases in muscle mass and strength observed with this type of training, but endurance training did not change capillary density ratio in muscle mass cross-sectional area (38). It is likely that activating GH-IGF1-PI3K pathway after muscle contraction is a main responsible for angiogenesis, a hormonal axis that previously verified as a major angiogenic regulator (10, 11, 13).
The other finding was a positive significant correlation between angiogenic factors, especially VEGF and GH in both training groups. According to this positive correlation, It appears that elevation of each of these factors can stimulate the other one (30), which in turn increases hypoxia stimulant factors through the activation of the PI3K-AKT and NO signaling pathway, ultimately resulting in an upregulation of angiogenic factor expression (11, 12). Previous studies suggested that NO acts as a downstream mediator of VEGF-stimulated angiogenesis (35, 39), but Ziche et al (1997) showed no significant correlation between bFGF and NO (39). Egginton et al (2009) reported that VEGF induces angiogenesis by upregulation of NO following shear stress, which commonly occurs in aerobic exercises; and upregulation of HIF following capillary and muscle stretch, which commonly raises up in resistance training (25).
This pathway causes increase in Hypoxia induced factor (HIF) through activation of PI3K-AKT, which increases the expression of HIF with inducing gene promoter region of VEGF, and probably promotes angiogenic factor genes expression (11, 12).
Interestingly, there is an inverse relationship between somatostatin with GH. Although somatostatin did not measure in this study, previous studies have indicated that somatostatin plays an inhibitory role in angiogenesis via VEGF suppression. McArdle et al (2010) demonstrated that increases in somatostatin in response to acute exercise inhibits VEGF production in endothelial cells (40). It is likely that increased GH reduces somatostatin, which is in line with positive increases in VEGF levels in CRT and TRT. In addition, as resistance training in healthy individuals simultaneously increases IL-1, Il-6, IL-10, TNF-α by recruiting big muscle masses led to higher inflammatory factors response and GH rises subsequently, then It makes the sense of VEGF increases (36, 41).
One of the limitations of present study was an inability to monitor the capillary density of subjects. Moreover, the findings can only apply to the specific CRT and TRT protocols utilized, and the effects of other training programs are unknown. Therefore, future studies may focus on effects of various kinds of TRT and CRT on angiogenesis and follow the angiogenesis axis to its practical effects on sport performances.