Further evidence for the role of Ang-(1-7)/Mas in the pathophysiology of the heart came from experimental protocols utilizing mice with genetic deficiency of Mas. They revealed that the cardiac function is impaired in Mas knockout mice likely due to the increased extracellular matrix proteins deposition in the heart [66, 73] . This profibrotic phenotype may be related to changes in matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) levels and/or activities [74, 75] .