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Therapeutic Perspectives of Angiotensin-(1-7) in the Treatment of Cardiovascular Disease

In the last decade, new biologically active components of the renin-angiotensin system were found. Angiotensin-(1-7) (Ang-(1-7)), a metabolite of angiotensin I and angiotensin II (Ang II), is considered the most pleiotropic component of the renin-angiotensin system, acting as a counterregulatory mediator of Ang II. Ang-(1-7) exerts beneficial effects on the cardiovascular system, including reduction of blood pressure, myocardial antihypertrofic and antifibrotic actions, and reversal of renal dysfunction, among others. Recent discovery of enzymatic pathways involved in Ang-(1-7) synthesis, such as the angiotensin-converting enzyme-2 (ACE2) and the existence of a specific receptor to this heptapeptide, the Mas receptor, have increased interest in the design of therapeutic strategies aimed at increasing the biological actions of Ang-(1-7). ACE inhibitors, AT1 receptor blockers and aldosterone antagonists enhance Ang-(1-7) levels by different mechanisms. Actually, non-peptidic Ang-(1-7) agonists and ACE2 activators are under development and could have a role in the treatment of cardiovascular diseases. The aim of the present review is to describe the biochemical and physiological actions of Ang-(1-7), the therapeutic strategies designed to enhance Ang-(1-7) activity foccusing in their possible role and limitations in the treatment of cardiovascular disease.