POP ablation blunted the increase in plasma Ang-(1-7) after Ang II infusion compared with wild-type mice (309 vs 472 fmol/mL, P=0.01), showing POP is the main conversion enzyme in circulation.
Prolyloligopeptidase (POP), rather than ACE2, is the primary enzyme responsible for converting Angiotensin II to Angiotensin-(1-7) in the circulation and lungs.
Absolute Event Rate: 309% vs 472%
p-value: p=0.01
The Ang II (Angiotensin II)-Angiotensin-(1-7) axis of the Renin Angiotensin System encompasses 3 enzymes that form Angiotensin-(1-7) Ang-(1-7) directly from Ang II: ACE2 (angiotensin-converting enzyme 2), PRCP (prolylcarboxypeptidase), and POP (prolyloligopeptidase). We investigated their relative contribution to Ang-(1-7) formation in vivo and also ex vivo in serum, lungs, and kidneys using models of genetic ablation coupled with pharmacological inhibitors. In wild-type (WT) mice, infusion of Ang II resulted in a rapid increase of plasma Ang-(1-7). In ACE2 −/− / PRCP −/− mice, Ang II infusion resulted in a similar increase in Ang-(1-7) as in WT (563±48 versus 537±70 fmol/mL, respectively), showing that the bulk of Ang-(1-7) formation in circulation is essentially independent of ACE2 and PRCP. By contrast, a POP inhibitor, Z-Pro-Prolinal reduced the rise in plasma Ang-(1-7) after infusing Ang II to control WT mice. In POP −/− mice, the increase in Ang-(1-7) was also blunted as compared with WT mice (309±46 and 472±28 fmol/mL, respectively P =0.01), and moreover, the rate of recovery from acute Ang II-induced hypertension was delayed ( P =0.016). In ex vivo studies, POP inhibition with ZZP reduced Ang-(1-7) formation from Ang II markedly in serum and in lung lysates. By contrast, in kidney lysates, the absence of ACE2, but not POP, obliterated Ang-(1-7) formation from added Ang II. We conclude that POP is the main enzyme responsible for Ang II conversion to Ang-(1-7) in the circulation and in the lungs, whereas Ang-(1-7) formation in the kidney is mainly ACE2-dependent.
Serfózó et al. (2019) studied Ang II conversion. POP ablation (POP-/-) or POP inhibitor (Z-Pro-Prolinal) vs. Wild-type mice was evaluated on Plasma Ang-(1-7) formation after Ang II infusion (p=0.01). POP ablation blunted the increase in plasma Ang-(1-7) after Ang II infusion compared with wild-type mice (309 vs 472 fmol/mL, P=0.01), showing POP is the main conversion enzyme in circulation.