Protective Role of the ACE2/Ang-(1–9) Axis in Cardiovascular Remodeling

Figure 3

Signaling events and cellular effects induced by Ang II via AT1R and opposing effects of Ang-(1–9) acting through AT2R. Proposed Ang-(1–9)-dependent mechanisms that antagonize the cardiovascular remodeling effects of Ang II. ACE2 can directly cleave Ang I to form Ang-(1–9). This peptide activates the AT2R to initiate signaling pathways that antagonize AT1R-mediated tyrosine kinase cascades. In this simplified scenario, Ang-(1–9) increases SHP-1 tyrosine phosphatase activity to inactivate src-dependent signaling. AT2R activation also acts other pathways such as NO-AKT. AT1R: Ang II type 1 receptor; AT2R: Ang II type 2 receptor; ERK1/2: extracellular signal-regulated kinase 1/2; JAK: Janus-activated kinase; MAPK: mitogen-activated protein kinase; p38: p38 MAPK; PKC: protein kinase C; STAT: signal transducer and activator of transcription; NO: nitric oxide; SHP-1: protein tyrosine phosphatase SH2 domain-containing phosphatase 1; MEK: mitogen/ERK kinase. Solid arrows indicates activation broken arrows indicates inactivation.