Involvement of α3 integrin/tetraspanins complexes in the angiogenic response induced by angiotensin II

The effect of angiotensin II (Ang II) on endothelial cell (EC) function has important potential implications, both under physiological conditions and in the pathogenesis of different cardiovascular diseases. We studied the effect of Ang II on EC junctions and its possible functional consequences. We found that Ang II induced a remarkable change on human umbilical vein endothelial cells (HUVEC) in the distribution of alpha3beta1 integrin and CD151, CD9 tetraspanins on cell membrane, with an important decrease of these molecular complexes at intercellular contacts. However, the morphology of EC, the integrins located at cell-substratum contact areas, the components of adherens and tight-junctions, as well as the barrier functions of EC monolayers, remained unchanged after Ang II exposure. The Ang II effect on alpha3beta 1/tetraspanins complexes was associated with a significant induction of angiotube formation by HUVEC in an in vitro model of capillary formation on Matrigel. The effect of Ang II was mediated through the angiotensin II receptor 1 AT1 receptor and was inhibited with antibodies specific for the alpha3 integrin chain, which indicates the critical role of this integrin in the angiogenic effect of Ang II. These results show that Ang II exerts a direct and very specific effect on EC lateral junctions that is selectively associated with the induction of angiogenesis by this peptide.