Angiotensin (1-7), a heptapeptide found in the heart and kidney, inhibits angiotensin-converting enzyme (ACE) in plasma and atrial tissue with an IC50 of 3.0 and 4.0μM, respectively[1]. Angiotensin (1-7) has been identified as regulating blood pressure, cardiac function and smooth muscle and myocardial cell growth as well as renal function regulation[2]. Angiotensin (1-7) has been extensively studied for modulation of vascular function in various cellular and animal models[3].
In vitro, Angiotensin (1-7) treatment (1nM; 48h) effectively reduced the proliferation of DU-145 prostate cancer cells and induced a significant reduction in the expression of MKI67[4]. Treatment of mouse podocytes with Angiotensin (1-7) at 10μM for 24 hours reversed high glucose-induced reduction of podocyte viability, increase of podocyte apoptosis, reduction of nephrin, podocin, WT-1 and MasR protein expression, and up-regulation of AT1R expression[5]. Angiotensin (1-7) treatment (1.7μM; 18 hours) effectively reduced tube formation in human umbilical vein endothelial cells[6].
In vivo, Angiotensin (1-7) treatment via daily intraperitoneal injection at 2mg/kg ameliorated sepsis-induced cardiomyopathy in mice by reducing inflammatory response and mitochondrial damage through NF-κB and MAPK pathways[7]. A single dose of 45μg/kg Angiotensin (1-7) administration via gavage promoted the resolution of lipopolysaccharide-induced pleurisy in mice by reducing neutrophil numbers and M1 inflammatory macrophage frequency after 24h treatment[8].
References:
[1] Roks A J M, Van Geel P P, Pinto Y M, et al. Angiotensin-(1–7) is a modulator of the human renin-angiotensin system[J]. Hypertension, 1999, 34(2): 296-301.
[2] Padda R S, Shi Y, Lo C S, et al. Angiotensin-(1-7): a novel peptide to treat hypertension and nephropathy in diabetes?[J]. Journal of diabetes & metabolism, 2015, 6(10): 10.4172/2155-6156.1000615.
[3] Durand M J, Zinkevich N S, Riedel M, et al. Vascular actions of angiotensin 1–7 in the human microcirculation: novel role for telomerase[J]. Arteriosclerosis, Thrombosis, and Vascular Biology, 2016, 36(6): 1254-1262.
[4] Domińska K, Okła P, Kowalska K, et al. Angiotensin 1–7 modulates molecular and cellular processes central to the pathogenesis of prostate cancer[J]. Scientific Reports, 2018, 8(1): 15772.
[5] Lu J, Chen G, Shen G, et al. Ang-(1-7) attenuates podocyte injury induced by high glucose in vitro[J]. Archives of Endocrinology and Metabolism, 2023, 67: e000643.
[6] Anton L, Merrill D C, Neves L A A, et al. Angiotensin-(1–7) inhibits in vitro endothelial cell tube formation in human umbilical vein endothelial cells through the AT1–7 receptor[J]. Endocrine, 2007, 32(2): 212-218.
[7] Chen X S, Cui J R, Meng X L, et al. Angiotensin-(1–7) ameliorates sepsis-induced cardiomyopathy by alleviating inflammatory response and mitochondrial damage through the NF-κB and MAPK pathways[J]. Journal of Translational Medicine, 2023, 21(1): 2.
[8] de Carvalho Santuchi M, Dutra M F, Vago J P, et al. Angiotensin‐(1‐7) and alamandine promote anti‐inflammatory response in macrophages in vitro and in vivo[J]. Mediators of Inflammation, 2019, 2019(1): 2401081.
Angiotensin (1-7)是一种存在于心脏和肾脏的七肽，在血浆和心房组织中抑制血管紧张素转换酶(ACE)的IC50值分别为3.0和4.0μM[1]。Angiotensin (1-7)已被证实具有调节血压、心脏功能、平滑肌和心肌细胞生长以及肾功能的作用[2]。在多种细胞和动物模型中，Angiotensin (1-7)对血管功能的调节功能已被广泛研究[3]。
在体外，1nM浓度的Angiotensin (1-7)处理48小时能有效抑制DU-145前列腺癌细胞的增殖，并显著降低MKI67的表达[4]。用10μM浓度的Angiotensin (1-7)处理小鼠足细胞24小时，可逆转高糖环境导致的足细胞活力下降、细胞凋亡增加、nephrin/podocin/WT-1/MasR的蛋白表达降低，以及AT1R表达上调等现象[5]。1.7μM浓度的Angiotensin (1-7)处理18小时能有效抑制人脐静脉内皮细胞的管腔形成[6]。
在体内，每日腹腔注射2mg/kg剂量的Angiotensin (1-7)可通过NF-κB和MAPK通路减少炎症反应和线粒体损伤来改善脓毒症诱导的小鼠心肌病[7]。单次45μg/kg剂量的Angiotensin (1-7)经灌胃给药24小时后，能促进脂多糖诱导的小鼠胸膜炎的消退，表现为中性粒细胞数量和M1型炎症巨噬细胞频率的降低[8]。