Angiotensin-(1-7)

Research-Grade

Angiotensin-(1-7) [Ang-(1-7)] is a seven-amino-acid peptide (Asp-Arg-Val-Tyr-Ile-His-Pro) generated from angiotensin II by the carboxypeptidase ACE2 (angiotensin-converting enzyme 2) and from angiotensin I by endopeptidases including neprilysin and thimet oligopeptidase. It functions as the primary effector of the protective arm of the renin-angiotensin system (RAS), acting through the G-protein-coupled Mas receptor (MasR) to counterbalance the vasoconstrictive, pro-inflammatory, pro-fibrotic, and pro-thrombotic effects of angiotensin II signaling through the AT1 receptor. This counter-regulatory axis — ACE2/Ang-(1-7)/Mas — has emerged as one of the most important cardioprotective pathways in cardiovascular physiology and a major therapeutic target in hypertension, heart failure, fibrotic disease, and metabolic syndrome. The biological effects of Ang-(1-7) are remarkable in their breadth and consistency across preclinical models. In the cardiovascular system, it produces vasodilation (via nitric oxide and prostaglandin release), reduces cardiac hypertrophy, inhibits vascular smooth muscle proliferation, and attenuates myocardial fibrosis following infarction. In the kidneys, it promotes natriuresis, opposes angiotensin II-mediated glomerular damage, and reduces proteinuria. Metabolically, Ang-(1-7) enhances insulin signaling and glucose uptake in skeletal muscle, improves pancreatic beta-cell function, and reduces hepatic steatosis in animal models of metabolic syndrome. Anti-inflammatory effects include suppression of NF-κB-mediated cytokine production, reduction of leukocyte adhesion to endothelium, and attenuation of oxidative stress through NADPH oxidase inhibition. These effects have been demonstrated across rodent models, large-animal studies, and ex vivo human tissue preparations. The ACE2/Ang-(1-7) axis gained enormous public attention during the COVID-19 pandemic because SARS-CoV-2 uses ACE2 as its cellular entry receptor. Viral binding to ACE2 downregulates membrane ACE2 expression, reducing Ang-(1-7) production and shifting the RAS balance toward the harmful angiotensin II/AT1 axis. This ACE2 depletion hypothesis has been proposed as a mechanism underlying COVID-19-related cardiovascular injury, acute lung injury, and coagulopathy. Clinical trials investigating recombinant ACE2 and exogenous Ang-(1-7) administration in COVID-19 patients were initiated, though results have been mixed. Beyond COVID-19, Ang-(1-7) formulations (including the cyclodextrin-encapsulated oral form and subcutaneous injection) have been tested in small clinical trials for pulmonary arterial hypertension, heart failure, and diabetic nephropathy, with Phase 1/2 data suggesting safety and preliminary efficacy signals that await confirmation in larger trials.