A 779 TFA is a potent antagonist of angiotensin-(1-7) receptor

A 779通过抑制由Ang II上调的增殖细胞核抗原（PCNA）蛋白表达来发挥作用，但A 779本身并不诱导VSMCs的增殖和迁移。使用Ang-(1-7)预处理显著抑制Ang II诱导的VSMCs炎症反应，这种炎症反应与MCP-1、VCAM-1和IL-1β的表达上调有关，而这种Ang-(1-7)的效果被A 779阻断。但是，A 779本身对VSMCs的炎症反应无影响[1]。

A 779通过抑制Ang1-7信号通路显著消除了卡托普利对骨代谢、矿化和微结构的保护效果。此外，A 779还恢复了去卵巢(OVX)对RANKL表达及ACE-1/AngII/AT1R信号通路的影响，并下调了OPG表达和ACE-2/Ang1-7/Mas通路。与临床观察到的ACE-1抑制后骨保护属性一致，局部激活ACE-2/Ang1-7/Mas信号和抑制成骨细胞生成似乎是卡托普利骨保护效应的负责机制，这可能在治疗残疾性骨病和骨骼肌肉疾病中具有潜在的治疗价值[2]。

HUVECs were cultured in vitro and divided into six groups:?the control group (normal medium), the ox-LDL group(treated with 75 mg/L ox-LDL), the ox-LDL+ Ang-(1-7) group (1 μmol/L Ang-(1-7) pretreated for 30 minutes, then intervened with 75 mg/L ox-LDL), the ox-LDL+ Ang-(1-7)+ A-779 group(1 μmol/L A-779 (Mas receptor) pretreated for 30 minutes, 1 μmol/L Ang-(1-7) pretreated for 30 minutes, then intervened with 75 mg/L ox-LDL), the ox-LDL+ A-779 group (1 μmol/L A-779 pretreated for 30 minutes, then intervened with 75 mg/L ox-LDL),?the ox-LDL+ HTA125 group (10 μg/L HTA125 (TLR4-blocking antibody) pretreated for 30 minutes, then intervened with 75 mg/L ox-LDL ).?The corresponding index was detected after 24 hours after intervention.?Apoptosis of cells were detected by Annexin V-FITC/PI double staining flow cytometry and transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL).?The generation of reactive oxygen species (ROS), products in oxidative stress, were detected by DCFH-DA staining.?The mRNA and protein expression levels of NADPH oxidase 4(NOX4) and TLR4 were detected by real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting analysis respectively[1].