Angiotensin-(1–7) and Vascular Function
The Clinical Context
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See related article, pp 185–191
It is now well established that the renin–angiotensin system (RAS) comprises 2 axes: (1) the classical axis comprising angiotensin-converting enzyme (ACE)–angiotensin II (Ang II)–Ang II type 1 receptor (AT1R) and (2) the recently characterized ACE2–Ang-(1–7)–mitochondrial assembly receptor (MasR) axis1,2 (Figure). Physiologically, both systems likely play a coordinated role in regulating cardiovascular function. Hyperactivation of the ACE–Ang II–AT1R axis generally causes deleterious effects, such as vasoconstriction, endothelial dysfunction, inflammation, fibrosis, thrombosis, and angiogenesis and is prohypertensive, whereas activation of the ACE2–Ang-(1–7)–MasR axis of the RAS opposes effects of the classical system and accordingly has been described as the protective arm of the RAS.2 Recent evidence indicates that Ang-(1–7) also mediates part of its cardioprotective effects by acting as an endogenous β-arrestin–biased agonist at the AT1R.3 In addition to MasR, it has been suggested that Ang-(1–7) binds Mas-related G proteins, such as MyrD (Mas-related G-protein–coupled receptor D).4 However, whether this is functionally significant remains to be confirmed, especially in humans.
Ang-(1–7) induces vasodilatory, anti-inflammatory, antifibrotic, antiangiogenic, and antihypertensive effects by binding to its G-protein–coupled MasR. Ang-(1–7) also improves glucose and lipid homeostasis.2 These …