Mouse aortic ring assay: A new approach of the molecular genetics of angiogenesis

Abstract

Angiogenesis, a key step in many physiological and pathological processes, involves proteolysis of the extracellular matrix. To study the role of two enzymatic families, serineproteases and matrix metalloproteases in angiogenesis, we have adapted to the mouse, the aortic ring assay initially developed in the rat. The use of deficient mice allowed us to demonstrate that PAI-1 is essential for angiogenesis while the absence of an MMP, MMP-11, did not affect vessel sprouting. We report here that this model is attractive to elucidate the cellular and molecular mechanisms of angiogenesis, to identify, characterise or screen "pro-or anti-angiogenic agents that could be used for the treatment of angiogenesis-dependent diseases. Approaches include using recombinant proteins, synthetic molecules and adenovirus-mediated gene transfer.

3-Bromophenyl 6-acetoxymethyl-2-oxo-2H-1-benzopyran-3-carboxylate inhibits cancer cell invasion in vitro and tumour growth in vivo

“…Thus, the observed activity of the coumarin derivatives on HT1080 cell invasion could not be ascribed to their inhibitory activity against the enzymes tested. Both compounds were found to be unable to inhibit the angiogenesis evaluated in the aortic ring assay (data not shown) according to the procedure previously described (Blacher et al, 2001;Masson et al, 2002). Consequently, further experimental investigations are required to determine the exact mechanism of action of the bromo coumarin derivative and its biological target.…”

Higher sensitivity of Adamts12-deficient mice to tumor growth and angiogenesis

“…We applied three models of angiogenesis, which have been previously successfully used to evaluate the contribution of different metalloproteinases during angiogenic processes (Masson et al, 2002;Berndt et al, 2006Berndt et al, , 2008. The transplantation system is a highly sensitive tool to inspect the kinetic of early steps of host stromal response to tumor signals (Mueller and Fusenig, 2004;Jost et al, 2007Jost et al, , 2008.…”

In vitro assays of angiogenesis for assessment of angiogenic and anti-angiogenic agents

“…The mouse aortic ring assay was developed to take advantage of the transgenic tools available for this species (Masson et al, 2002). Angiogenesis assays can be conducted using endothelial cells with specific characteristics or labels; for example, aortas from mice whose endothelial cells express green-fluorescent protein can be used to facilitate visualization of vessel outgrowth (Zhu et al, 2003).…”

“…Angiogenesis assays can be conducted using endothelial cells with specific characteristics or labels; for example, aortas from mice whose endothelial cells express green-fluorescent protein can be used to facilitate visualization of vessel outgrowth (Zhu et al, 2003). Angiogenic outgrowth occurs over a shorter time period with the mouse aortic rings (Masson et al, 2002), and both angiogenic and anti-angiogenic factors can be assessed (e.g. Kojima et al, 2007;van der Schaft et al, 2002).…”