TY - JOUR
AU1 - Wang, Hsueh-Hsiao
AU2 - Wu, Yih-Jer
AU3 - Tseng, Ya-Ming
AU4 - Su, Cheng-Huang
AU5 - Hsieh, Chin-Ling
AU6 - Yeh, Hung-I
AB - Background We investigated the contribution of mitochondrial dysfunction to the senescence of human endothelial progeni- tor cells (EPCs) expanded in vitro and the underlying molecular mechanism. Methods and results Serial passage increased cell doubling time and those cells reaching the doubling time for more than 100% were defined as senescent EPCs, of which the activity of therapeutic angiogenesis was attenuated in mouse ischemic hindlimbs. The senescent cells, in medium free of glucose and bicarbonate, showed impaired activity in migration and tube formation. Flow cytometry indicated increased content of reactive oxygen species, mitochondria, and calcium, while bio- energetic analysis showed increased oxygen consumption and reduced ATP content. Examination of mitochondrial network showed that senescence increased the length of the network and ultrastructure analysis exhibited elongated mitochondria. Immunoblotting of the senescent EPCs demonstrated decreased expression level of fission protein1 (Fis1). In rat EPCs, the Fis1 level was decreased in the animals aged 24 months or older, compared to those of 3 months. Silencing of Fis1 in the young EPCs using Fis1-specific siRNA leads to appearance of phenotype resembling those of senescent cells, including elevated oxidative stress, disturbed mitochondrial network, reduced mitochondria membrane potential, decreasing ATP con- tent, lower proliferation activity, and loss of therapeutic 
TI - Mitochondrial fission protein 1 up-regulation ameliorates senescence-related endothelial dysfunction of human endothelial progenitor cells
JF - Angiogenesis
DO - 10.1007/s10456-019-09680-2
DA - 2019-09-03
UR - https://www.deepdyve.com/lp/springer-journals/mitochondrial-fission-protein-1-up-regulation-ameliorates-senescence-s0kBiGN62Q
SP - 569
EP - 582
VL - 22
IS - 4
DP - DeepDyve
ER -