Background: Dipeptidyl peptidase 4 (DPP4) is known to be present in many tissues, including endothelium and it was shown that the inhibition of DPP4 activity may improve cardiovascular profile. There are indications that the IGF system is related to type 2 diabetes and the presence of coronary atherosclerosis. This finding opens new possibilities for treatment of cardiovascular diseases by using therapeutic options which may reduce DPP4 and IGF activity.
Purpose: To evaluate the effect of exercise training on DPP4 and circulating IGF binding protein 1 (IGF BP1) levels, and to assess their relationship with nitric oxide (NOx)- circulating blood marker of endothelial function, in patients with stable coronary artery disease (CAD).
Methods: 48 subjects: 28 pts with stable CAD (CAD group; 59.2±8.2 years) and 20 healthy controls (C group; 57.1±8.2 years) were studied. At baseline in all pts and controls, values of DPP4, IGF BP1 and NOx by peripheral vein sampling, were evaluated and exercise test was performed. After the initial study, all patients underwent a supervised 3 weeks exercise training at residential center, and after that period values of DPP4, IGF BP1 and NOx, as well as exercise tolerance were determined again.
Results: Baseline value of DPP4 and IGF BP1 was significantly higher in CAD than in C group (P=0.023 and P=0.021), while NOx was lower (60.81±10.93 vs 77.28±29.86 μg/L P=0.032). After 3 weeks of exercise training DPP4 decreased significantly in CAD group (from 751.42±250.86 to 617.87±216.14 μg/L, P=0.002), as well as IGF BP1 (P=0.026) and NOx inreased (P=0.028). Those changes resulted in no significant difference in DPP4, IGF BP1 and NOx after three weeks between CAD and C group. Exercise capacity (METs) at baseline was significantly lower in CAD than in C group (P<0.001), and it significantly increase in CAD group after exercise period (P<0.001).A positive correlation during exercise period was found between IGF BP1 decrease and NOx increase (r=0.890, P<0.001), between IGF BP1 decrease and DPP 4 decrease (r=0.920, P<0.001), between IGF BP1 decrease and METs increase (r=0.878, P<0.001), between DPP 4 decrease and NOx increase (r=0.965, P<0.001), between DPP 4 decrease and METs increase (r=0.818, P<0.001), and between METs increase and NOx increase (r=0.827, P<0.001).
Conclusion: Regular exercise training in patients with CAD leads to significant reduction of DPP4, and IGF BP1 level and increase of NOx level. There is a positive correlation between decrease in DPP4 and decrease in IGF BP1, between decrease in DPP4 and increase in NOx and decrease in IGF BP1 and increase in NOx.