4.5 Article

The Angiotensin-(1-12)/Chymase axis as an alternate component of the tissue renin angiotensin system

Journal

MOLECULAR AND CELLULAR ENDOCRINOLOGY
Volume 529, Issue -, Pages -

Publisher

ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2020.111119

Keywords

Renin-angiotensin system; Angiotensinogen; Angiotensin peptides; Angiotensin-(1-12); Angiotensin I; Angiotensin II; Renin; Chymase; Angiotensin-converting enzyme; Metabolism

Funding

  1. National Heart, Lung and Blood Institute of the NIH [P01 HL-051952]

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The discovery of the dodecapeptide angiotensin-(1-12) as an alternate form of angiotensin I has shed light on noncanonical mechanisms for renin independent generation of angiotensins. Studies have confirmed the presence of Ang-(1-12) in multiple organs in both humans and rats, serving as a substrate for Ang II formation. Research has shown that angiotensin II can be generated from angiotensin-(1-12) without the involvement of renin, with chymase playing a key role in this conversion process.
The identification of an alternate extended form of angiotensin I composed of the first twelve amino acids at the N-terminal of angiotensinogen has generated new knowledge of the importance of noncanonical mechanisms for renin independent generation of angiotensins. The human sequence of the dodecapeptide angiotensin-(1-12) [NAsp(1)-Arg(2)-Val(3)-Tyr(4)-Ile(5)-His(6)-Pro(7)-Phe(8)-His(9)-Leu(10)-Val(11)-Ile(12)-COOH] is an endogenous substrate that in the rat has been documented to be present in multiple organs including the heart, brain, kidney, gut, adrenal gland, and the bone marrow. Newer studies have confirmed the existence of Ang-(1-12) as an Ang II-forming substrate in the blood and heart of normal and diseased patients. Studies to-date document that angiotensin II generation from angiotensin-(1-12) does not require renin participation while chymase rather than angiotensin converting enzyme shows high catalytic activity in converting this tissue substrate into angiotensin II directly.

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