Mol. Hum. Reprod. Advance Access originally published online on February 25, 2005
Molecular Human Reproduction 2005 11(4):253-260; doi:10.1093/molehr/gah159
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In utero angiopoietin-2 gene delivery remodels placental blood vessel phenotype: a murine model for studying placental angiogenesis
1Center for Reproductive Sciences, Department of Obstetrics, Gynecology and Reproductive Sciences, 2UCSF Comprehensive Cancer Center, University of California and 3Department of Pathology, University of California, San Francisco, CA, USA
4 To whom correspondence should be addressed at: Box 0556, 505 Parnassus, Center for Reproductive Sciences, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, CA 94143-0556, USA. E-mail: jaffer{at}obgyn.ucsf.edu
Angiopoietin (Ang)-2, the natural antagonist of the Ang1/Tie2 receptor is a complex regulator of blood vessel plasticity that plays a pivotal role in both vessel sprouting [in the presence of vascular endothelial growth factor (VEGF)-A] and vessel regression (in the absence of VEGF-A). Based on the spatial and temporal expression of Ang2 throughout human gestation, we recently suggested that the Ang2 may play a pivotal role in placental angiogenesis. Further, to examine this tenet we have developed a novel murine model system in which in utero Ang2 gene delivery via a non-replicating adenoviral expression vector has the potential to manipulate the blood vessel phenotype in vivo during pregnancy. Ang2 overexpression selectively and rapidly remodels the labyrinth perivascular extracellular matrix, subsequently promoting plasticity of the maternal and fetal vessels, which appear honeycombed due to a 2-fold increase in blood vessel luminal area. High levels of Ang2 impair endothelial cell adhesiveness, leading to vascular leakiness with perivascular oedema, which increases placental weight. These observations suggest that the Ang2 overexpression may play a key role in placental vascular remodelling. Furthermore, we suggest a novel new model to study the pathobiology of placental vascularization and the effect of placental blood vessels on fetal phenotype.
Key words: angiogenesis/angiopoietin-2/placenta
This study was supported, in part, by a Serono Foundation Fellowship in Reproductive Endocrinology (to E. Geva). This work is in partial fulfillment of the requirements of the PhD degree for E. Geva, MD, Weizmann Institute of Science, Rehovot, Israel. Presented in part at the 49th Annual Meeting of the Society for Gynecologic Investigation, 19–22 March 2002, Los Angeles, CA, USA.
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