Angiotensinogen is encoded by the gene AGT and is a glycoprotein secreted by hepatocytes that is cleaved renin to yield angiotensin I, which is further cleaved to generate angiotensin II.
Angiotensinogen is the rate limiting factor in the production of angiotensin II and links angiotensinogen and angiotensin II to hypertension.
The greater the copy of the angiotensinogen gene, the higher the blood pressure.
Plasma angiotensinogen levels correlate with blood pressure in hypertension and its overexpression is a hallmark of hypertension with endothelial dysfunction, cardiac hypertrophy and renal abnormalities.
Angiotensinogen is the most proximal component of the angiotensin system.
Circulating angiotensinogen is derive primarily from the liver.
Zilebesiran is a siRNA that targets the AGT gene in the liver and post-transcriptionally silences its expression leading to a decreased production of angiotensinigen protein, suppressed synthesis of angiotensin I, and angiotensin II and consequently blood pressure lowering.