Angiogenesis effect of Astragalus polysaccharide combined with endothelial progenitor cells therapy in diabetic male rat following experimental hind limb ischemia

Background Diabetes mellitus (DM) is a common disease accompanied with a high incidence of hind limb ischemia (HLI). In recent years, numerous studies demonstrated that endothelial progenitor cells (EPCs) are involved in angiogenesis and maintenance of vascular integrity following HLI. On the other side, it has been proved that Astragalus polysaccharide (APS) could promote angiogenesis. In the present study, we aimed to evaluate the effect of APS and EPCs on enhancing angiogenesis after experimental HLI caused by femoral artery ligation in rats with streptozotocin (STZ)-induced diabetes. Methods Rats (n=110) were randomly assigned to the following groups: sham group, ischemia group, APS group, EPCs group and APS+EPCs group. APS, EPCs or an equal volume of vehicle was administered intramuscularly after HLI induction, and 6 rats were assessed by angiography at 28 days after induction of HLI, 6 rats were sacrificed at the same time point to take histological studies; biochemical tests were also performed at that point in the rest rats. Results APS or EPCs treatment induced an increase, respectively, in the protein expression of vascular endothelial growth factor (VEGF) (36.61%, 61.59%), VEGF receptor-1 (VEGFR-1) (35.50%, 57.33%), VEGFR-2 (31.75%, 41.89%), Angiopoietin-1 (Ang-1) (37.57%, 64.66%) and Tie-2 (42.55%, 76.94%) (P <0.05), after HLI injury. And combined therapy of APS and EPCs enhanced the effort of angiogenesis after HLI induction in diabetic rats, through elevating protein expression of VEGF (99.67%), VEGFR-1 (105.33%), VEGFR2 (72.05%), Ang-1 (114.30%) and Tie-2 (111.87%) (P<0.05). Similarly, mRNA expression of VEGF, VEGFR-1, VEGFR2, Ang-1, Tie-2 also show similar trends as well as protein expression (P<0.05). Conclusion APS or EPCs could enhance angiogenesis, and the combined treatment leads to better effort, at least, partially via VEGFNEGFR and Ang-1/Tie-2 signaling pathway.