Molecular and Pathophysiological Features of Angiotensinogen: A Mini Review

Abstract

The renin-angiotensin system is an essential regulatory system for blood pressure and fluid homeostasis. Angiotensinogen is the only known precursor of all the peptides generated in this system. While many of the basic understandings of angiotensinogen have come from research efforts to define its role in blood pressure regulation, novel pathophysiological functions of angiotensinogen have been discovered in the last two decades including kidney developmental abnormalities, atherosclerosis, and obesity. Despite the impressive advance in the understanding of angiotensinogen gene structure and protein functions, some fundamental questions remain unanswered. In this short review, we provide contemporary insights into the molecular characteristics of angiotensinogen and its pathophysiological features. In light of the recent progress, we emphasize some newly recognized functional features of angiotensinogen other than its regulation on blood pressure.

Figure 1. Schematic Representation of Human AGT Gene and Protein

Human angiotensinogen (AGT) gene contains 5 exons. Exon 2 encodes the majority of the protein. After the removal of a 33 aa signal peptide, the 452 aa mature AGT is secreted. Cleavage of mature AGT by renin gives a decapeptide, AngI, and the 442 aa des(AngI)-AGT. AngI is further cleaved by angiotensin-converting enzyme (ACE) into an octapeptide, AngII. Two cysteines at 18 and 138 form a disulphide bridge (Cys18-Cys138) that confers a conformational change allowing access of renin to the AngI cleavage site of AGT. Diagrams were drawn proportional to actual gene and protein size based on the University of California Santa Cruz Human Genome Browser Feb 2009 Assembly. UTR: untranslated region; CDS: coding sequences; ACE: angiotensin-converting enzyme.