Newer Insights into the Biochemical Physiology of the Renin–Angiotensin System: Role of Angiotensin-(1-7), Angiotensin Converting Enzyme 2, and Angiotensin-(1-12)

Ferrario, Carlos M.; Jessup, Jewell A.; Varagic, Jasmina

Knowledge of the mechanisms by which the rennin–angiotensin system contributes to cardiovascular pathology continues to advance at a rapid pace as newer methods and therapies uncover the nature of this complex system and its fundamental role in the regulation of blood pressure and tissue function. The characterization of the biochemical pathways and functions mediated by angiotensin-(1-7) [Ang-(1-7)], angiotensin converting enzyme 2 (ACE2), and the mas receptor has revealed a vasodepressor and antiproliferative axis that within the rennin–angiotensin system opposes the biological actions of angiotensin II (Ang II). In addition, new research expands on this knowledge by demonstrating additional mechanisms for the formation of Ang II and Ang-(1-7) through the existence of an alternate form of the angiotensinogen substrate [angiotensin-(1-12)] which generates Ang II and even Ang-(1-7) through a non-renin dependent action. Altogether, this research paves the way for a better understanding of the intracellular mechanisms involved in the synthesis of angiotensin peptides and its consequences in terms of cell function in both physiology and pathology.