Reduction of connexin43 in human endothelial progenitor cells impairs the angiogenic potential.
Our previous work showed that arsenic trioxide down-regulated Cx43 and attenuated the angiogenic potential of human late endothelial progenitor cells (EPC). However, the relation between Cx43 and angiogenic activity of the EPC remained unclear. In the study, human late EPC were treated with siRNA specific to Cx43 (Cx43siRNA). The expression profiles as well as activity of the treated cells were examined. In parallel, the angiogenic potential of human EPC treated with Cx43siRNA was evaluated using murine hind limb ischemic model. The results showed that, in the EPC treated with Cx43siRNA, the activity of migration, proliferation, and angiogenic potential were attenuated, accompanied by reduction in vascular endothelial growth factor (VEGF) expression. In hind limb ischemia mice, EPC treated with Cx43siRNA lost the therapeutic angiogenic potential. VEGF supplementation partially recovered the activity impaired by Cx43 down-regulation. In conclusion, reduced Cx43 expression per se in the EPC causes decreased expression of VEGF and impaired angiogenic potential of the cells. Prevention of Cx43 reduction is a potential target to maintain the angiogenic potential of the EPC.
Department of Medicine, Mackay Medical College, No. 46, Sec. 3, Zhongzheng Rd, Sanzhi District, New Taipei City 252, Taiwan.
Hsueh-Hsiao
HH
Wang
Cheng-Huang
CH
Su
Yih-Jer
YJ
Wu
Jiun-Yi
JY
Li
Ya-Ming
YM
Tseng
Yi-Chun
YC
Lin
Chin-Ling
CL
Hsieh
Cheng-Ho
CH
Tsai
Hung-I
HI
Yeh
D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D015153:Blotting, Western; D001973:Bromodeoxyuridine; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D013234:Stem Cells / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D018952:Antigens, CD34; D018031:Connexin 43; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A; D001973:Bromodeoxyuridine