A 779 is a potent and selective angiotensin-(1-7)/Mas receptor antagonist with an IC50 value of 0.3nM[1]. Angiotensin-(1–7) (Ang-(1-7)) is an endogenous ligand for the G protein-coupled receptor, a bioactive peptide within the renin-angiotensin system (RAS) that significantly contributes to maintaining cardiovascular homeostasis and hydroelectrolyte balance in physiological and pathologic conditions[1][2]. A 779 inhibit the biological effects of Ang-(1-7) by binding to the G protein-coupled receptor Mas receptor (MasR)[3].
In vitro, pretreatment of human umbilical vein endothelial cells (HUVECs) with 1μM A 779 for 30 minutes significantly inhibited Ang-(1-7)’s effect on attenuating ox-LDL induced injury by modulating the specific Mas receptors[4]. Treatment of mouse islet β-cell line MIN6 cells with 1nM A 779 for 48h reverse Ang-(1-7) ’s effect on preventing high glucose-induced pathological dedifferentiation of pancreatic β-cell[5].
In vivo, A 779 considerably eradicate the defensive properties of Ang-(1-7) on bone metabolism, mineralization and micro-structure after it was delivered at infusion rate of 400ng kg−1 min−1 for 6 weeks in an ovariectomized (OVX) rodent model of osteoporosis[6][7]. Subcutaneous injection of A 779(80μg/kg) block the inhibitory effects of angiotensin converting enzyme 2 (ACE2) on endoplasmic reticulum stress (ERS) and pyroptosis in Ventilator-induced lung injury[8].
References:
[1] Santos RA, Simoes e Silva AC, Maric C, et al. Angiotensin-(1-7) is an endogenous ligand for the G protein-coupled receptor Mas. Proc Natl Acad Sci U S A. 2003;100(14):8258-8263.
[2] Maia LG, Ramos MC, Fernandes L, de Carvalho MH, Campagnole-Santos MJ, Souza dos Santos RA. Angiotensin-(1-7) antagonist A-779 attenuates the potentiation of bradykinin by captopril in rats. J Cardiovasc Pharmacol. 2004;43(5):685-691.
[3 Santos RA, Campagnole-Santos MJ, Baracho NC, et al. Characterization of a new angiotensin antagonist selective for angiotensin-(1-7): evidence that the actions of angiotensin-(1-7) are mediated by specific angiotensin receptors. Brain Res Bull. 1994;35(4):293-298.
[4] Yan WF, Xue JJ, Yang HY, Liang B, Yang ZM. 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;45(3):223-229.
[5] Guo H, Guo D, An M, Zhang R, Wang C, He J. Angiotensin-(1-7) Improves Islet β-cell Dedifferentiation by Activating PI3K/Akt/FoxO1 Pathway. Protein Pept Lett. 2023;30(12):1009-1019.
[6] Abuohashish HM, Ahmed MM, Sabry D, Khattab MM, Al-Rejaie SS. 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;7(1):2293.
[7] Abuohashish HM, Ahmed MM, Sabry D, Khattab MM, Al-Rejaie SS. ACE-2/Ang1-7/Mas cascade mediates ACE inhibitor, captopril, protective effects in estrogen-deficient osteoporotic rats. Biomed Pharmacother. 2017;92:58-68.
[8] Lin X, Zhuang Y, Gao F. ACE2 Alleviates Endoplasmic Reticulum Stress and Protects against Pyroptosis by Regulating Ang1-7/Mas in Ventilator-Induced Lung Injury. Front Biosci (Landmark Ed). 2024;29(9):334.
A 779是一种有效的选择性血管紧张素-(1-7)/ Mas受体拮抗剂，IC50值为0.3nM[1]。血管紧张素-(1-7)(Ang-(1-7))是G蛋白偶联受体的内源性配体，是肾素-血管紧张素系统（RAS）中的一种生物活性肽，在生理和病理条件下对维持心血管稳态和水电解质平衡有重要作用[1][2]。A 779通过与G蛋白偶联受体MasR结合抑制Ang-(1-7) 的生物学效应[3]。
在体外实验中，1μM A 779预处理人脐静脉内皮细胞（HUVECs）30min，可通过调节特异性Mas受体显著抑制Ang-(1-7) 减弱ox-LDL诱导的损伤的作用[4]。用1nM A 779处理小鼠胰岛β-细胞系MIN6细胞48小时，可逆转Ang-(1-7)抑制高糖诱导的胰腺β-细胞病理性去分化的作用[5]。
在体内，在去卵巢（OVX）啮齿动物骨质疏松模型中以400ng kg−1 min−1的速率持续输注A 779 6周后，A 779显著消除了Ang-（1-7）对骨代谢、微结构和矿化的保护作用[6][7]。在呼吸机所致肺损伤小鼠模型中，皮下注射A 779（80μg/kg）可阻断血管紧张素转换酶2 （ACE2）对内质网应激（ERS）和焦亡的抑制作用[8]。