Angiotensinogen (AGT) (AGT)

Angiotensinogen (AGT) is a 452-amino acid glycoprotein primarily synthesized and secreted by hepatocytes into the circulation, serving as the essential precursor for the renin-angiotensin-aldosterone system (RAAS) (UniProt P01019). It is cleaved by the enzyme renin in the rate-limiting step of the RAAS cascade to produce angiotensin I, which is further processed into the potent vasoconstrictor angiotensin II (StatPearls: Renin Angiotensin Aldosterone System). Angiotensin II regulates systemic blood pressure, fluid homeostasis, and electrolyte balance; however, its overproduction is a central driver of primary hypertension and associated organ damage in the heart and kidneys (PubMed: 32853455). Emerging therapeutic approaches, such as the siRNA zilebesiran, utilize GalNAc-conjugation to specifically target AGT mRNA in hepatocytes for degradation (NEJM: 10.1056/NEJMoa2215851). By depleting the systemic reservoir of the precursor protein at its source, these therapies provide a long-acting mechanism to lower blood pressure and mitigate cardiovascular risk. This hepatocyte-targeted approach aims to improve patient compliance and provide more consistent blood pressure control compared to daily oral RAAS inhibitors.

Other names

Serpin A8SERPINA8Serpin peptidase inhibitor clade A member 8Pre-angiotensinogenAlpha-2-globulin

RNA interference (siRNA) or antisense oligonucleotide (ASO) mediated degradation of AGT mRNA specifically in hepatocytes, resulting in the suppression of systemic angiotensinogen protein synthesis and subsequent reduction of downstream RAAS peptides.