Both ACE and ACE2 are increased in the failing heart [18] [19] [20] . ACE2 expression has consistently been seen to be up-regulated in the peri-infarct area after MI [10, 20, 33] and in end stage heart failure [34] indicative of a role in injury. Knockout of the ace2 gene increases MMP2 and MMP9 levels in the peri-infarct region of mice, resulting in disruption of the extracellular matrix and enhanced adverse remodelling [10] . ACE2 over-expression has been shown to inhibit collagen production in response to hypoxic injury [35] . Moreover, activation of remodelling pathways has been demonstrated in ace2 knockout animals in the absence of an increase in Ang II [36] . Cardiac remodelling is a key pathological process in the development of heart failure. Integrins play a key role in this process by mediating cell-ECM interactions and cellular signalling. ITGB1 has also been implicated in myocardial dysfunction [28] . An association between ITGB1 and ACE2 has previously been reported in the failing heart and attributed to the presence of an RGD motif in ACE2 [25] . We have established that both ACE and ACE2 binds ITGB1 and also its common cardiac binding partner, ITGA5 [37] , as well as the RGD-independent and liver rich ITGA2 [38] . However, in contrast to the study of Lin et al. [25] our data clearly suggest that these interactions occur independently of an RGD motif. 3-dimensional modelling has demonstrated that the RGD motif present in the ectodomain of ACE2 is inaccessible, which explains its redundancy in integrin binding. The aspartate residue is positioned facing the active site cleft of the protein and as such is not available to bind into the integrin binding pocket [39] . Given the structural homology between the two proteins, it is not surprising that ACE is also capable of binding integrins as the interaction appears to be independent of the RGD sequence, which is lacking in ACE.