A potential role for islet-1 in post-natal angiogenesis and vasculogenesis.
The LIM-homeobox transcription factor islet-1 (Isl1) marks a cell population which gives rise to myocardial, pacemaker, endothelial and smooth muscle cells, which are derived from the secondary heart field during heart embryogenesis. Isl1+ precursors have the potential of self-renewal and differentiation into endothelial, cardiomyocyte and smooth muscle lineages. The primary objective of this study was to determine whether retroviral gene delivery of Isl1 to endothelial cells and mesenchymal stem cells (MSCs) could promote angiogenic and vasculogenic properties. To this end, endothelial cells and rat MSCs were retrovirally transduced to express Isl1. Isl1 expression in endothelial cells resulted in enhanced proliferation and adhesion to fibronectin. In addition, increased IL-1b and VEGF secretion was evident in Isl1 transduced endothelial cells, concomitant with increased migratory and tube formation properties of the endothelial cells. Isl1 expression in MSCs promoted their vasculogenic properties and resulted in enhanced in vitro tube formation. Finally, Isl1 expressing endothelial cells induced enhanced in vivo vascularisation in C57BL/6J mice. These data suggest, for the first time, that Isl1 promotes postnatal angiogenesis and vasculogenesis by improving the angiogenic properties of endothelial cells and MSCs.
Barzelay
Aya
A
Cardiovascular Research Center, The Department of Cardiology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Ben-Shoshan
Jeremy
J
Entin-Meer
Michal
M
Maysel-Auslender
Sofia
S
Afek
Arnon
A
Barshack
Iris
I
Keren
Gad
G
George
Jacob
J
D000818:Animals; D002448:Cell Adhesion; D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation; D017077:Culture Media, Conditioned / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism* / Q000637:transplantation; D005353:Fibronectins / Q000378:metabolism; D005822:Genetic Vectors; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics; D053583:Interleukin-1beta / Q000378:metabolism; D060850:LIM-Homeodomain Proteins; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic; D010641:Phenotype; D051381:Rats; D017208:Rats, Wistar; D012190:Retroviridae / Q000235:genetics; D013997:Time Factors; D014157:Transcription Factors; D014161:Transduction, Genetic; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D017077:Culture Media, Conditioned; D005353:Fibronectins; D018398:Homeodomain Proteins; D053583:Interleukin-1beta; D060850:LIM-Homeodomain Proteins; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; C063843:insulin gene enhancer binding protein Isl-1; C467480:vascular endothelial growth factor A, mouse