| Title : Donepezil can improve ischemic muscle atrophy by activating angiomyogenic properties of satellite cells - Noguchi_2014_Circ.J_78_2317 |
| Author(s) : Noguchi T , Kakinuma Y , Arikawa M , Okazaki K , Hoshino E , Iiyama T , Kubo T , Kitaoka H , Doi Y , Sato T |
| Ref : Circ J , 78 :2317 , 2014 |
| Abstract : BACKGROUND: Saving more limbs of patients with peripheral arterial disease (PAD) from amputation by accelerating angiogenesis in affected limbs has been anticipated for years. We hypothesized that an anti-Alzheimer drug, donepezil (DPZ), can activate angiomyogenic properties of satellite cells, myogenic progenitors, and thus be an additional pharmacological therapy against PAD.Methods and Results:In a murine hindlimb ischemia model, we investigated the angiogenic effects of a clinical dose of DPZ (0.2 mg.kg(-1).day(-1)) and its combination with cilostazol, a platelet aggregation inhibitor and a conventional therapeutic drug against PAD. The combination therapy most effectively improved skin coldness and most effectively upregulated vascular endothelial growth factor (VEGF)-producing satellite cells in ischemic hindlimbs. Computed tomography revealed that DPZ remarkably attenuated ischemic muscle atrophy and induced super-restoration in affected hindlimbs. The in vitro study with human aortic endothelial cells showed that DPZ or its combination with cilostazol effectively upregulated the expression of pAkt, hypoxia inducible factor-1alpha, and VEGF protein. Likewise, in primary cultured satellite cells, DPZ, alone or in combination, upregulated the expression of VEGF, interleukin-1beta, and fibroblast growth factor 2 protein. CONCLUSIONS: The present results suggest that a clinical dosage of DPZ accelerates angiomyogenesis by directly acting on both endothelial and satellite cells. Therefore, DPZ is a potential additional choice for conventional drug therapy against PAD. (Circ J 2014; 78: 2317-2324). |
| ESTHER : Noguchi_2014_Circ.J_78_2317 |
| PubMedSearch : Noguchi_2014_Circ.J_78_2317 |
| PubMedID: 25070503 |
Noguchi T, Kakinuma Y, Arikawa M, Okazaki K, Hoshino E, Iiyama T, Kubo T, Kitaoka H, Doi Y, Sato T (2014)
Donepezil can improve ischemic muscle atrophy by activating angiomyogenic properties of satellite cells
Circ J
78 :2317
Noguchi T, Kakinuma Y, Arikawa M, Okazaki K, Hoshino E, Iiyama T, Kubo T, Kitaoka H, Doi Y, Sato T (2014)
Circ J
78 :2317