Oudit GY, Wang K, Viveiros A, Kellner MJ, Penninger JM. Angiotensin-converting enzyme 2-at the heart of the COVID-19 pandemic. Cell. 2023;186(5):906–22. https://doi.org/10.1016/j.cell.2023.01.039.
Article CAS PubMed PubMed Central Google Scholar
Osman IO, Melenotte C, Brouqui P, Million M, Lagier JC, Parola P, et al. Expression of ACE2, soluble ACE2, Angiotensin I, Angiotensin II and Angiotensin-(1–7) is modulated in COVID-19 patients. Front Immunol. 2021;12:625732. https://doi.org/10.3389/fimmu.2021.625732.
Article CAS PubMed PubMed Central Google Scholar
Mori J, Patel VB, Abo Alrob O, Basu R, Altamimi T, Desaulniers J, et al. Angiotensin 1–7 ameliorates diabetic cardiomyopathy and diastolic dysfunction in db/db mice by reducing lipotoxicity and inflammation. Circ Heart Fail. 2014;7(2):327–39. https://doi.org/10.1161/CIRCHEARTFAILURE.113.000672.
Article CAS PubMed Google Scholar
Mori J, Patel VB, Ramprasath T, Alrob OA, DesAulniers J, Scholey JW, et al. Angiotensin 1–7 mediates renoprotection against diabetic nephropathy by reducing oxidative stress, inflammation, and lipotoxicity. Am J Physiol Ren Physiol. 2014;306(8):F812–21. https://doi.org/10.1152/ajprenal.00655.2013.
Raizada MK, Ferreira AJ. ACE2: a new target for cardiovascular disease therapeutics. J Cardiovasc Pharmacol. 2007;50(2):112–9. https://doi.org/10.1097/FJC.0b013e3180986219.
Article CAS PubMed Google Scholar
Prasad R, Floyd JL, Dupont M, Harbour A, Adu-Agyeiwaah Y, Asare-Bediako B, et al. Maintenance of enteral ACE2 prevents diabetic retinopathy in type 1 diabetes. Circ Res. 2023;132(1):e1–21. https://doi.org/10.1161/CIRCRESAHA.122.322003.
Article CAS PubMed Google Scholar
Verma A, Shan Z, Lei B, Yuan L, Liu X, Nakagawa T, et al. ACE2 and Ang-(1–7) confer protection against development of diabetic retinopathy. Mol Ther. 2012;20(1):28–36. https://doi.org/10.1038/mt.2011.155.
Article CAS PubMed Google Scholar
Chappell MC, Marshall AC, Alzayadneh EM, Shaltout HA, Diz DI. Update on the Angiotensin converting enzyme 2-Angiotensin (1–7)-MAS receptor axis: fetal programing, sex differences, and intracellular pathways. Front Endocrinol (Lausanne). 2014;4:201. https://doi.org/10.3389/fendo.2013.00201.
Article PubMed PubMed Central Google Scholar
Montezano AC, Kuriakose J, Hood KY, Sin YY, Camargo LL, Namkung Y, et al. Ang-(1–7) and ET-1 interplay through Mas and ET(B) receptor interaction defines a novel vasoprotective mechanism. Hypertension. 2025;82(2):267–81. https://doi.org/10.1161/HYPERTENSIONAHA.124.22693.
Article CAS PubMed Google Scholar
Rivas-Santisteban R, Lillo J, Munoz A, Rodriguez-Perez AI, Labandeira-Garcia JL, Navarro G, et al. Novel interactions involving the Mas receptor show potential of the renin-angiotensin system in the regulation of microglia activation: altered expression in Parkinsonism and dyskinesia. Neurotherapeutics. 2021;18(2):998–1016. https://doi.org/10.1007/s13311-020-00986-4.
Article CAS PubMed PubMed Central Google Scholar
Kuriakose J, Montezano AC, Touyz RM. ACE2/Ang-(1–7)/Mas1 axis and the vascular system: vasoprotection to COVID-19-associated vascular disease. Clin Sci (Lond). 2021;135(2):387–407. https://doi.org/10.1042/CS20200480.
Article CAS PubMed PubMed Central Google Scholar
Zhao S, Sun W, Jiang P. Role of the ACE2/Ang-(1–7)/Mas axis in glucose metabolism. Rev Cardiovasc Med. 2021;22(3):769–77. https://doi.org/10.31083/j.rcm2203083.
Miller AJ, Bingaman SS, Mehay D, Medina D, Arnold AC. Angiotensin-(1–7) improves integrated cardiometabolic function in aged mice. Int J Mol Sci. 2020;21(14):5131. https://doi.org/10.3390/ijms21145131.
Article CAS PubMed PubMed Central Google Scholar
Self WH, Shotwell MS, Gibbs KW, de Wit M, Files DC, Harkins M, et al. Renin-Angiotensin system modulation with synthetic angiotensin (1–7) and angiotensin II type 1 Receptor–Biased ligand in adults with COVID-19: two randomized clinical trials. JAMA. 2023;329(14):1170–82. https://doi.org/10.1001/jama.2023.3546%J.
Echeverria-Rodriguez O, Gallardo-Ortiz IA, Del Valle-Mondragon L, Villalobos-Molina R. Angiotensin-(1–7) participates in enhanced skeletal muscle insulin sensitivity after a bout of exercise. J Endocr Soc. 2020;4(2):bvaa007. https://doi.org/10.1210/jendso/bvaa007.
Article CAS PubMed PubMed Central Google Scholar
Lu Y, Xing C, Lv X, Zhang C, Liu G, Chen F, et al. Changes of ACE2 in different glucose metabolites and its relationship with COVID-19. Medicine (Baltimore). 2022;101(41):e31102. https://doi.org/10.1097/MD.0000000000031102.
Article CAS PubMed PubMed Central Google Scholar
Sanyal AJ, Bedossa P, Fraessdorf M, Neff GW, Lawitz E, Bugianesi E, et al. A phase 2 randomized trial of Survodutide in MASH and fibrosis. N Engl J Med. 2024;391(4):311–9. https://doi.org/10.1056/NEJMoa2401755.
Article CAS PubMed Google Scholar
Matthew Morris E, Fletcher JA, Thyfault JP, Rector RS. The role of angiotensin II in nonalcoholic steatohepatitis. Mol Cell Endocrinol. 2013;378(1–2):29–40. https://doi.org/10.1016/j.mce.2012.04.013.
Article CAS PubMed Google Scholar
Rajapaksha IG, Gunarathne LS, Asadi K, Laybutt R, Andrikopoulous S, Alexander IE, et al. Angiotensin converting enzyme-2 therapy improves liver fibrosis and glycemic control in diabetic mice with fatty liver. Hepatol Commun. 2022;6(5):1056–72. https://doi.org/10.1002/hep4.1884.
Article CAS PubMed Google Scholar
Nunes-Souza V, Alenina N, Qadri F, Mosienko V, Santos RAS, Bader M, et al. ACE2 knockout mice are resistant to high-fat diet-induced obesity in an age-dependent manner. Int J Mol Sci. 2024. https://doi.org/10.3390/ijms25179515.
Article PubMed PubMed Central Google Scholar
Penninger JM, Grant MB, Sung JJY. The role of angiotensin converting enzyme 2 in modulating gut microbiota, intestinal inflammation, and coronavirus infection. Gastroenterology. 2021;160(1):39–46. https://doi.org/10.1053/j.gastro.2020.07.067.
Article CAS PubMed Google Scholar
Song L, Ji W, Cao X. Integrated analysis of gut microbiome and its metabolites in ACE2-knockout and ACE2-overexpressed mice. Front Cell Infect Microbiol. 2024;14:1404678. https://doi.org/10.3389/fcimb.2024.1404678.
Article CAS PubMed PubMed Central Google Scholar
Smail SW, Albarzinji N, Salih RH, Taha KO, Hirmiz SM, Ismael HM, et al. Microbiome dysbiosis in SARS-CoV-2 infection: implication for pathophysiology and management strategies of COVID-19. Front Cell Infect Microbiol. 2025;15:1537456. https://doi.org/10.3389/fcimb.2025.1537456.
Article CAS PubMed PubMed Central Google Scholar
Bredon M, Hausfater P, Khalki L, Tijani Y, Cheikh A, Brot L, et al. Gut microbiota alterations are linked to COVID-19 severity in North African and European populations. NPJ Biofilms Microbiomes. 2025;11(1):106. https://doi.org/10.1038/s41522-025-00733-7.
Article CAS PubMed PubMed Central Google Scholar
Wang P, Guo R, Bai X, Cui W, Zhang Y, Li H, et al. Sacubitril/Valsartan contributes to improving the diabetic kidney disease and regulating the gut microbiota in mice. Front Endocrinol (Lausanne). 2022;13:1034818. https://doi.org/10.3389/fendo.2022.1034818.
Article PubMed PubMed Central Google Scholar
Tian E, Wang F, Zhao L, Sun Y, Yang J. The pathogenic role of intestinal flora metabolites in diabetic nephropathy. Front Physiol. 2023;14:1231621. https://doi.org/10.3389/fphys.2023.1231621.
Article PubMed PubMed Central Google Scholar
Lin J, Nie Q, Cheng J, Zhong YN, Zhang T, Zhang X, et al. A microbial amino-acid-conjugated bile acid, tryptophan-cholic acid, improves glucose homeostasis via the orphan receptor MRGPRE. Cell. 2025;188(17):4530–e4825. https://doi.org/10.1016/j.cell.2025.05.010.
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