# Angiotensinogeen als nieuw aangrijppunt bij hypertensie: opkomst van RNA-medicijnen (zilebesiran, tonlamarsen)

*geplaatst 2026-03-19 · Hypertensie · Hypertension · doi https://www.ahajournals.org/doi/abs/10.1161/HYPERTENSIONAHA.125.26091 · https://hartvaat.nl/2026/03/19/angiotensinogeen-als-nieuw-aangrijppunt-bij-hypertensie-opkomst-van-rna-medicijn/*

Hypertensie is de belangrijkste beïnvloedbare risicofactor voor hart- en vaatziekten. Angiotensinogeen (AGT) is een centraal onderdeel van het renine-angiotensine-aldosteronsysteem (RAAS), maar werd lang gezien als een passief substraat in plaats van een actief aangrijppunt — anders dan ACE en de angiotensine II-receptor. Dit overzicht beschrijft de moleculaire biologie en regulatie van AGT, genetische varianten (zoals M235T en −6G>A) en de rol bij zoutgevoelige hypertensie, obesitas-gerelateerde ontsteking en 'RAAS-escape'. Vooral relevant zijn de nieuwe RNA-gebaseerde middelen die AGT remmen: het small-interfering-RNA zilebesiran en het antisense-oligonucleotide tonlamarsen, die in trials een langdurige bloeddrukdaling met een gunstig veiligheidsprofiel laten zien. AGT komt zo naar voren als een veelbelovend, bovenstrooms doelwit en biomarker — met potentie voor langwerkende behandeling van (resistente) hypertensie en betere therapietrouw.

## English: Angiotensinogen Reconsidered: Evolving Perspectives in Hypertension Research

Hypertension is the leading modifiable risk factor for cardiovascular disease. Angiotensinogen (AGT) is a central component of the renin-angiotensin-aldosterone system (RAAS) but was long viewed as a passive substrate rather than an active target — unlike ACE and the angiotensin II receptor. This review describes the molecular biology and regulation of AGT, genetic variants (such as M235T and −6G>A) and its role in salt-sensitive hypertension, obesity-related inflammation and 'RAAS escape'. Especially relevant are the new RNA-based agents that inhibit AGT: the small interfering RNA zilebesiran and the antisense oligonucleotide tonlamarsen, which show prolonged blood-pressure reduction with a favourable safety profile in trials. AGT thus emerges as a promising upstream target and biomarker — with potential for long-acting treatment of (resistant) hypertension and better adherence.

## Abstract (original, from the publication)

Hypertension, Volume 83, Issue 6, Page e26091, June 1, 2026. Hypertension is the leading modifiable risk factor for cardiovascular disease, stroke, chronic kidney disease, and premature mortality. Although AGT (angiotensinogen) is a central component of the renin-angiotensin-aldosterone system, it was historically viewed primarily as a biochemical substrate rather than an active regulator of blood pressure and received less attention as a therapeutic target in hypertension compared with downstream renin-angiotensin-aldosterone system components such as angiotensin-converting enzyme and angiotensin II receptors. However, emerging evidence highlights its dynamic, tissue-specific role in blood pressure regulation and its responsiveness to metabolic, hormonal, and inflammatory stimuli. This narrative review examines the molecular biology, structure-function relationships, and regulatory mechanisms of AGT, including genetic variants such as M235T and −6G>A, which contribute to interindividual and population-level susceptibility to hypertension. We further explore AGT’s pathogenic role in salt-sensitive hypertension, obesity-related inflammation, and renin-angiotensin-aldosterone system escape phenomena. Recent translational advances, including RNA-based therapeutics such as small interfering RNAs (zilebesiran) and antisense oligonucleotides (tonlamarsen), demonstrate promising blood pressure reductions and favorable safety profiles in clinical trials. AGT also shows potential as a biomarker for hypertensive nephropathy and treatment responsiveness. This review underscores the value of AGT as an upstream therapeutic target and diagnostic marker, offering new avenues for precision medicine and long-acting strategies in the management of both conventional and resistant hypertension while possibly addressing medication adherence-related obstacles.

Auteurs: Mehmet Kanbay

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Bron: Hypertension, https://doi.org/https://www.ahajournals.org/doi/abs/10.1161/HYPERTENSIONAHA.125.26091. Bijgewerkt 2026-07-03T18:39:23Z. Citeer vrij, met bronvermelding en een link naar hartvaat.nl (de url van het record). Samenvattingen zijn redactioneel werk van HartVaat; de oorspronkelijke publicaties blijven van hun uitgevers (doi). Geen medisch advies.