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Angiotensinogen Reconsidered: Evolving Perspectives in Hypertension Research
Mehmet Kanbay1, Mustafa Guldan2, Lasin Ozbek2
1Division of Nephrology, Department of Internal Medicine (M.K.), Koc University School of Medicine, Istanbul, Turkey.
Hypertension (Dallas, Tex. : 1979)
|March 19, 2026
Summary
Angiotensinogen (AGT) is a key regulator of blood pressure, not just a substrate. Targeting AGT offers new therapeutic strategies for hypertension and related conditions.
Area of Science:
- Cardiovascular Medicine
- Molecular Biology
- Genetics
Background:
- Hypertension is a major modifiable risk factor for cardiovascular diseases.
- Angiotensinogen (AGT) has emerged as a critical regulator of blood pressure, beyond its historical view as a mere substrate.
- Its role is dynamic, tissue-specific, and influenced by metabolic, hormonal, and inflammatory factors.
Purpose of the Study:
- To review the molecular biology, structure-function, and regulation of AGT.
- To explore the role of AGT genetic variants in hypertension susceptibility.
- To examine AGT's involvement in salt-sensitive hypertension, obesity, and RAAS escape.
Main Methods:
- Narrative review of existing literature.
- Analysis of molecular biology and genetic data related to AGT.
- Evaluation of translational advances in AGT-targeted therapies.
Main Results:
- AGT genetic variants (M235T, -6G>A) are linked to hypertension susceptibility.
- AGT plays a pathogenic role in salt-sensitive hypertension and obesity-related inflammation.
- RNA-based therapeutics (zilebesiran, tonlamarsen) show promising blood pressure reduction and safety.
Conclusions:
- AGT is a valuable upstream therapeutic target for hypertension.
- AGT serves as a potential biomarker for hypertensive nephropathy and treatment response.
- Targeting AGT offers new precision medicine and long-acting strategies for hypertension management, potentially improving adherence.
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