Figure 1.

Tissue renin–angiotensin system cascade. Prorenin is activated by the (pro)renin receptor ((P)RR) and possibly by proteolysis, to cleave angiotensin (Ang) I from angiotensinogen (AGT). Angiotensin-converting enzyme (ACE) then converts Ang I to the biologically active Ang II. Ang II can bind to angiotensin II type 1 receptor (AGTR1) to promote proliferation, angiogenesis, fibrosis, migration and invasion through stimulation of growth factors and intracellular signalling pathways. Furthermore, angiotensin (Ang) II binds to angiotensin II type 2 receptor (AGTR2) and antagonises AGTR1 activation. Ang I can also be further converted by angiotensin-converting enzyme 2 (ACE2) to Ang(1–7). Ang(1–7) acts upon its receptor Mas. This results in antagonism of Ang II/AGTR1 stimulation, thus inhibiting proliferation, angiogenesis, fibrosis, migration and invasion.