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Involvement of Endothelial Small GTPase RhoA in Angiogenesis In Vitro and In Vivo
Author(s) -
Zahra Fatema Tuz,
Sajib Md Sanaullah,
Ichiyama Yusuke,
Akwii Racheal,
Tullar Paul,
Kubota Yoshiaki,
Mikelis Constantinos M
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.477.14
Subject(s) - rhoa , angiogenesis , microbiology and biotechnology , cdc42 , biology , endothelial stem cell , neovascularization , cancer research , vascular endothelial growth factor a , signal transduction , vascular endothelial growth factor , in vitro , biochemistry , vegf receptors
Angiogenesis, the formation of new blood vessels, is a highly orchestrated process requiring a well‐regulated balance between pro‐angiogenic and anti‐angiogenic factors and corresponding signaling networks. It is an essential process during development and in specific adult conditions such as wound healing and ovulation. Imbalanced angiogenesis is a characteristic of several diseases such as cancer, inflammation, rheumatoid arthritis, osteoarthritis and age‐related macular degeneration. The Rho family of small GTPases plays a central role in a variety of cellular processes involving cytoskeletal rearrangement, cell movement, microtubule dynamics, signal transduction, gene expression which are necessary for vascular development and angiogenesis. Among the small GTPases of the Rho family, RhoA, Rac1 and Cdc42 are the best characterized. Although the role of endothelial Rac1 and Cdc42 in embryonic vascular development and retinal angiogenesis has been studied recently, the role of endothelial RhoA is yet to be explored. In this study, we aim to identify the involvement of endothelial RhoA in angiogenesis in vitro and in vivo . In vitro , RhoA seems to be involved in endothelial cell proliferation, cell migration, invasion and sprouting triggered by important angiogenesis inducers, such as Vascular Endothelial Growth Factor (VEGF) and Sphingosine‐1 Phosphate (S1P). To study the involvement of endothelial RhoA in vascular development in vivo , we generated endothelial‐specific RhoA deficiency through the Tie2‐Cre and Cdh5‐CreERT 2 promoters. In vivo deletion of RhoA in endothelial cells during embryogenesis leads to decreased survival of endothelial RhoA‐deficient mice. However, the few mutant survivors do not present morphological or behavioral abnormalities. In line with that, inducible RhoA deficiency in the retinal vessels in different developmental days did not affect the radial growth, the number of filopodia per area and the area with deep vascular plexus. Ongoing experiments aim to clarify the compensation mechanisms of RhoA deficiency in physiological angiogenesis in vivo versus in vitro models, providing a better understanding of the role of endothelial small GTPase RhoA in normal physiology and human diseases. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .