**Background**
The renin-angiotensin system (RAS) is a complex hormonal cascade critical for regulating blood pressure, fluid balance, and various inflammatory responses. While the classical AngII/AT1R axis is primarily associated with vasoconstriction and inflammation, the alternative ACE2/Ang-(1-7)/Mas receptor axis generally exerts counter-regulatory, protective effects. The Mas receptor, a G-protein coupled receptor, mediates the beneficial actions of Ang-(1-7), including anti-inflammatory and osteo-protective properties. Understanding the specific role of this axis is essential for developing therapies for cardiovascular diseases and metabolic bone disorders, such as osteoporosis. In this context, we will introduce a specific antagonist of the Mas receptor – A 779.
**Definition**
A 779 is a specific antagonist of the G-protein coupled Mas receptor, which is the primary receptor for Ang-(1-7). According to the A 779 description, it is a peptide-based compound with the molecular formula C39H60N12O11.
**In Vitro and In Vivo Studies**
The A 779 biological activity has been extensively evaluated in both cellular and animal models. In vitro studies demonstrate that A 779 inhibits the effects of Ang-(1-7), specifically blocking its ability to suppress the proliferating cell nuclear antigen (PCNA) protein expression that is up-regulated by Ang II. Furthermore, A 779 blocks the ability of Ang-(1-7) to retard Ang II-induced inflammatory responses in vascular smooth muscle cells (VSMCs), which are characterized by the up-regulation of MCP-1, VCAM-1, and IL-1β. Additionally, A 779 inhibits the Ang-(1-7)-mediated suppression of Akt and ERK1/2 phosphorylation induced by Ang II. Notably, A 779 alone does not induce proliferation, migration, or inflammatory responses in VSMCs.
In vivo research highlights the importance of the Mas receptor in bone metabolism. In ovariectomized (OVX) rats, A 779 in vivo administration (400 ng/kg/min, s.c.) for 6 weeks markedly elevated serum bone-specific alkaline phosphatase (BALP), telopeptides of collagen type I (CTX), tartarate-resistant acid phosphatase (TRAcP 5b), and osteocalcin (OC), as well as urinary deoxypyridinoline (DPD). By blocking the Mas receptor, A 779 abolished the favorable effects of Ang-(1-7) on bone health and eradicated the protective effects of captopril on bone mineralization and microstructure. It was further observed that A 779 restored OVX-induced effects on RANKL expression and the ACE-1/AngII/AT1R cascade while down-regulating the ACE-2/Ang1-7/Mas pathway. In conclusion, A 779 is a potent Mas receptor antagonist that serves as a critical tool for studying the ACE2/Ang-(1-7)/Mas axis in vascular and bone research.
Keywords
A 779, 159432-28-7, A779, A-779, Angiotensin Receptor, Inhibitor, inhibitor, inhibit
References
[1] Abuohashish HM, et al. Angiotensin (1-7) ameliorates the structural and biochemical alterations of ovariectomy-induced osteoporosis in rats via activation of ACE-2/Mas receptor axis. Sci Rep. 2017 May 23;7(1):2293.
[2] Abuohashish HM, et al. ACE-2/Ang1-7/Mas cascade mediates ACE inhibitor, captopril, protective effects in estrogen-deficient osteoporotic rats. Biomed Pharmacother. 2017 Aug;92:58-68.
[3] Yan WF, et al. Effects and related mechanism of angiotensin-(1-7) on Toll-like receptor 4-mediated oxidative stress in human umbilical vein endothelial cells. Zhonghua Xin Xue Guan Bing Za Zhi. 2017 Mar 24;45(3):223-229.