Ang‐(1–7) Induced MAS1 Receptor‐Mediated Angiogenesis in the Rat Microvasculature

Abstract

The renin‐angiotensin system influences hypertension and angiogenesis. Specifically, angiotensin II (AngII) has been shown to regulate angiogenesis and cause vasoconstriction, fibrosis, cellular growth, and migration through the AT1 receptor. Angiotensin 1–7 (Ang(1–7)), whose actions are mediated by the Mas1 receptor, can act antagonistically to AngII by inducing vasodilation, anti‐fibrotic, anti‐hypertrophic, and anti‐proliferative effects. However, Ang‐(1–7) induced MAS1 receptor signaling is much less defined than AngII signaling, especially during angiogenesis. Here we show that Ang‐(1–7) promotes angiogenesis in the microvasculature of the rat hind limb through the Mas1 receptor independently of AngII and the AT1 receptor. Additionally, we show in an ex vivo tube formation assay that Ang‐(1–7) induces an increased angiogenic response among rat microvascular endothelial cells. Utilizing advanced proteomic methodology, downstream components of the Mas1 receptor signaling pathway were also identified to determine possible signaling pathways in the angiogenic response. Signaling pathway components identified included proteins involved in nascent protein synthesis, exocytosis, and cellular reorganization, along with regulators of nitric oxide, G‐protein, and NF‐kappaB signaling.