Donepezil Can Improve Ischemic Muscle Atrophy by Activating Angiomyogenic Properties of Satellite Cells

Nicotinic receptor-dependent and -independent effects of galantamine, an acetylcholinesterase inhibitor, on the non-neuronal acetylcholine system in C2C12 cells

“…The accumulated evidence in several reports [20][21][22], other than our studies [1,2], strongly supported our findings. Compatible with the ChAT reporter assay results, galantamineinduced VEGF secretion was blunted by neither mecamylamine nor atropine; however, nicotine-induced VEGF secretion was completely suppressed by mecamylamine.…”

“…On the contrary, a few studies have disclosed the existence of an NNCS or NNA in skeletal muscle including the study performed by Hamann M et al [16], who reported that myoblasts and satellite cells synthesized ACh, however, did not mention that the system was pharmacologically upregulated. Therefore, the current study uncovered the important finding that muscle-derived cells are equipped with this system, which will be a therapeutic target for some cardiovascular disease, as suggested by our previous studies [2,3].…”

“…However, satellite cells play a crucial role in the regeneration of muscle, i.e., myogenesis, because they are considered to be myogenic stem cells [17]. Our previous study revealed that satellite cells as well as vascular endothelial cells were involved in accelerating angiogenesis in a murine hindlimb ischemia model [2,3]. In those studies, satellite cells were confirmed to be responsible for angiogenic factor expression.…”

“…We previously reported that donepezil, an anti-Alzheimer's drug, can accelerate angiogenesis by targeting endothelial cells [1]; further research disclosed that this acceleration of angiogenesis by donepezil is executed by both endothelial and satellite cells, i.e., myogenic stem cells, because satellite cells play powerful roles in producing angiogenic factors when they are activated from quiescent states [2,3]. Moreover, we elucidated the detailed molecular mechanisms using C2C12 cells, a murine myoblast cell line, which exhibited increased expression of angiogenic factors through nicotinic receptors [3].…”

Future perspectives of a cardiac non-neuronal acetylcholine system targeting cardiovascular diseases as an adjunctive tool for metabolic intervention

“…NNA-mediated ACh-induced HIF-1α is reported to be closely related to angiogenesis, because VEGF expression is increased by ACh. Based on these results, the source of NNA involved in angiogenesis can be represented by not only endothelial cells [22,23] but also myocytes, e.g., cardiomyocytes [24] and skeletal muscle [25][26][27]. The principal molecular mechanisms of angiogenesis may be through ACh-induced non-hypoxic HIF-1α stabilization leading to upregulation of VEGF [17,18,24].…”