Angiotensinogen (AGT) is the sole precursor of all angiotensin peptides. Although AGT is generally considered as a passive substrate of the renin–angiotensin system, there is accumulating evidence that the regulation and functions of AGT are intricate. Understanding the diversity of AGT properties has been enhanced by protein structural analysis and animal studies. In addition to whole-body genetic deletion, AGT can be regulated in vivo by cell-specific procedures, adeno-associated viral approaches and antisense oligonucleotides. Indeed, the availability of these multiple manipulations of AGT in vivo has provided new insights into the multifaceted roles of AGT. In this review, the combination of structural and functional studies is highlighted to focus on the increasing recognition that AGT exerts effects beyond being a sole provider of angiotensin peptides.

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Published in Hypertension Research, v. 39, issue 7, p. 492-500.

© 2016 Official journal of the Japanese Society of Hypertension

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A corrigendum to this article can be found at https://doi.org/10.1038/hr.2016.106.

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Our research work is supported by a grant from the National Institutes of Health (HL107319 to Alan Daugherty) and a pilot grant to Hong Lu by an Institutional Development Award from the National Institute of General Medical Sciences of the National Institutes of Health under grant number P20 GM103527.