P644Influence of exercise training on dipeptidyl peptidase 4 and stromal cell-derived factor 1 in patients with coronary artery disease: relationship to endothelial biomarker response

Abstract

Background: Dipeptidyl peptidase 4 (DPP4) exerts many functions on cardiovascular system and it was shown that the inhibition of DPP4 activity may improve cardiovascular profile. The chemokine stromal cell-derived factor 1 (SDF1) is able to home hematopoietic progenitor cells to injured areas of heart tissue, however elevated levels are associated with a risk of the extent of coronary artery disease (CAD). Those findings open new possibilities for treatment of cardiovascular diseases by using therapeutic options which may reduce DPP4 activity and SDF1 level. Purpose: To evaluate the impact of exercise training on DPP4 and SDF1, and to assess is there relationship between DPP4, SDF1 and circulating blood marker of endothelial function: Xanthine Oxidase (XO), in patients with CAD. Methods: 23 pts with stable CAD (CAD group; 55.2±6.8 years) and 19 healthy controls (C group; 55.1±8.0 years) were studied. At baseline in all pts and controls, values of DPP4, SDF1 and XO 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, SDF1 and XO as well as exercise tolerance were determined again. Results: Baseline value of DPP4 and SDF1 was significantly higher in CAD than in C group (P=0.008 and P<0.001). After 3 weeks of exercise training DPP4 decreased significantly in CAD group (from 792.03±260.08 to 573.11±173.63 μg/L, P<0.0005), as well as SDF1 (from 2570.06±387.07 to 2142.45±521.66 pg/mL, P<0.001) and XO (P<0.0005). Those changes resulted in no significant difference in DPP4 and SDF1 after three weeks between CAD and C group, while XO was still higher in CAD than in C group (P=0.001). Exercise capacity (METs) at baseline was significantly lower in CAD than in C group (P=0.016), and it significantly increase in CAD group after exercise period (P<0.0005). A positive correlation in difference achieved during exercise period was found between decrease in SDF1 and decrease in XO (r=0.728, p<0.001), between decrease in SDF1 and decrease in DPP4 (r=0.479, p=0.021), between decrease in SDF1 and increase in METs (r=0.734, p<0.001), between decrease in DPP4 and increase in METs (r=0.719, p<0.005), and between decrease in XO and decrease in DPP4 (r=0.581, p=0.004). Conclusion: Regular exercise training in patients with CAD leads to significant reduction of DPP4, SDF1 and amelioration of endothelial function. There is a positive correlation between decrease in SDF1 and decrease in DPP4, between decrease in SDF1 and decrease in XO, and between decrease in XO and decrease in DPP4.