Combination of simvastatin administration and EPC transplantation enhances angiogenesis and protects against apoptosis for hindlimb ischemia.
The aim of this present study is to investigate the impacts of combinatorial simvastatin administration and endothelial progenitor cell (EPC) transplantation on therapeutic angiogenesis in an athymic nude mouse model of hind limb ischemia. Athymic nude mice were divided into four groups (n = 10/group): vehicle administration plus PBS injection (control), simvastatin administration plus PBS injection (simvastatin), vehicle administration plus EPC transplantation (EPC), and simvastatin administration plus EPC transplantation (combination). The combination therapy had the greatest laser Doppler blood perfusion imager (LDPI) index and capillary density among the four groups. Importantly, this combination therapy significantly reduced apoptosis of ischemic skeletal muscle cells in part through downregulation of Bax and upregulation of Bcl-2 compared with the other groups. Moreover, the combination therapy exhibited the highest efficacy of increasing the ratio of phospho-Akt to Akt among the four groups. Taken together, the simvastatin and EPC combination therapy promotes powerful angiogenesis in hindlimb ischemia. The combination therapy not only inhibites apoptosis of ischemic skeletal muscle cells partially via downregulation of Bax and upregulation of Bcl-2, but also activates Akt phosphorylation significantly. These efficacies may be mediated by the angiogenic potency of simvastatin, EPCs, and by the beneficial effects of simvastatin on transplanted EPCs as well.
Hu
Zhengli
Z
Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China.
Zhang
Fumin
F
Yang
Zhijian
Z
Yang
Naiquan
N
Zhang
Dingguo
D
Zhang
Jinying
J
Cao
Kejiang
K
D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D042783:Endothelial Cells / Q000637:transplantation*; D006614:Hindlimb / Q000473:pathology; D007511:Ischemia / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D018919:Neovascularization, Physiologic; D019821:Simvastatin / Q000008:administration & dosage*; D033581:Stem Cell Transplantation / Q000379:methods*; D016896:Treatment Outcome; D015854:Up-Regulation
D051017:Apoptosis Regulatory Proteins; D019821:Simvastatin