Journal
EXPERIMENTAL BIOLOGY AND MEDICINE
Volume 241, Issue 17, Pages 1888-1899Publisher
SAGE PUBLICATIONS LTD
DOI: 10.1177/1535370216660211
Keywords
Angiotensin converting enzyme 2; angiotensin-(1-7); Mas receptor; finerenone; mineralocorticoid receptor coregulators; aldosterone synthase inhibitors
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Funding
- Polish Committee for Scientific Research [NN405 627938]
- Medical University of Bialystok [N/ST/MN/16/001/2226, N/ST/ZB/16/002/2226]
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The renin-angiotensin-aldosterone system (RAAS) is more complex than it was originally regarded. According to the current subject knowledge, there are two main axes of the RAAS: (1) angiotensin-converting enzyme (ACE)-angiotensin II-AT(1) receptor axis and (2) ACE2-angiotensin-(1-7)-Mas receptor axis. The activation of the first axis leads to deleterious effects, including vasoconstriction, endothelial dysfunction, thrombosis, inflammation, and fibrosis; therefore, blocking the components of this axis is a highly rational and commonly used therapeutic procedure. The ACE2-Ang-(1-7)-Mas receptor axis has a different role, since it often opposes the effects induced by the classical ACE-Ang II-AT(1) axis. Once the positive effects of the ACE2-Ang-(1-7)-Mas axis were discovered, the alternative ways of pharmacotherapy activating this axis of RAAS appeared. This article briefly describes new molecules affecting the RAAS, namely: recombinant human ACE2, ACE2 activators, angiotensin-(1-7) peptide and non-peptide analogs, aldosterone synthase inhibitors, and the third and fourth generation of mineralocorticoid receptor antagonists. The results of the experimental and clinical studies are encouraging, which leads us to believe that these new molecules can support the treatment of cardiovascular diseases as well as cardiometabolic disorders.
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