Fig. 1. The RAS is a complex system whose bioactive peptides signal through different receptors. The RAS is a complex system whose bioactive peptides signal.

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Fig. 1. The RAS is a complex system whose bioactive peptides signal through different receptors. The RAS is a complex system whose bioactive peptides signal through different receptors. Angiotensinogen (AGT), generated and released into circulation by the liver, is hydrolyzed by renin, a product of the kidneys’ juxtaglomerular cells, to form AngI. AngI is then hydrolyzed by ACE, predominantly expressed by endothelial cells in the vascular territory of the lungs, to form the biologically active AngII. In addition to AngII, other truncated bioactive peptides have been identified, such as AngIII, AngIV, Ang(1–7), Ang(1–9), AngA, and alamandine. AngII interacts with two seven-transmembrane receptors, AT1R and AT2R, both of which also mediate the effects of AngA. Ang(1–7) mainly acts via the MAS receptor (MASR), and alamandine binds and signals through MRGD (MAS-related G protein–coupled receptor D). IRAP (insulin-regulated membrane aminopeptidase; also known as AT4R) is a binding site for AngIV (1–7). APA, aminopeptidase A; APN, aminopeptidase N; DC, decarboxylase; MLDAD, mononuclear leukocyte-derived aspartate DC; NEP, neutral endopeptidase; PEP, prolyendopeptidase. Matthias Pinter and Rakesh K. Jain Sci Transl Med 2017;9:eaan5616 Published by AAAS