Clin Res Cardiol 101, Suppl 1, April 2012

P374 - Role for miR-223 in the regulation of angiogenesis
 
L. Shi1, B. Fißlthaler1, N. Zippel1, I. Fleming1
 
1Institut für Vascular Signalling, Klinikum der Goethe-Universität, Frankfurt am Main;
 
MiRNAs (miR) are endogenously expressed small non coding RNAs that play an important role in regulating target gene expression. Although the influence of several miRNAs on endothelial cell function has been reported, the diversity of miRNA expression between in vivo condition and in vitro cultures is still unclear.
To identify miRs that play a role in the regulation of endothelial cell differentiation /dedifferentiation we screened freshly isolated and cultured HUVEC. The miRNA profiling revealed that miR-223 is highly expressed in freshly isolated endothelial cells but dramatically decreased in cultured HUVEC (P1) and mouse lung endothelial cells. Overexpression of pre-miR-223 inhibited HUVEC migration in a scratch wound assay and transwell migration assay in response to VEGF or bFGF. There was no effect of miR-223 on HUVEC proliferation (BrdU incorporation assay). miR-223 overexpression inhibited HUVEC tube formation on Matrigel and prevented the formation of endothelial cell sprouts in a modified spheroid assay.   Moreover, in miR-223 knockout mice we detected an increased neovascularisation in Matrigel plugs containing VEGF and bFGF and accelerated recovery of perfusion after hind limb ischemia. Using a proteomic approach we found that eNOS and RhoB were downregulated by miR-223. 3’ UTR analysis suggested miR-223 directly targets RhoB and only indirectly affect eNOS expression. SiRNA mediated knockdown of RhoB expression reduced the ability of HUVEC to form tubular like structures on Matrigel.
Taken together, these results indicate that miR-223 maintains endothelial cells in an antiproliferative phenotype and may regulate endothelial cell differentiation and the quiescent in vivo phenotype.
 
Clin Res Cardiol 101, Suppl 1, April 2012
Zitierung mit Vortrags- oder Posternummer s.o.
DOI 10.1007/s00392-012-1100-6

http://www.abstractserver.de/dgk2012/ft/abstracts/P374.htm