{"id":"689fa66d1a42","type":"article","url":"https://hartvaat.nl/2026/03/19/angiotensinogeen-als-nieuw-aangrijppunt-bij-hypertensie-opkomst-van-rna-medicijn/","title":"Angiotensinogeen als nieuw aangrijppunt bij hypertensie: opkomst van RNA-medicijnen (zilebesiran, tonlamarsen)","title_en":"Angiotensinogen Reconsidered: Evolving Perspectives in Hypertension Research","category":"hypertensie","category_label":"Hypertensie","professions":["cardioloog","huisarts","internist"],"tags":["ace-remmers","angiotensinereceptorblokkers","bloeddrukbehandeling","ras-remmers"],"journal":"Hypertension","doi":"https://www.ahajournals.org/doi/abs/10.1161/HYPERTENSIONAHA.125.26091","source_url":"https://doi.org/https://www.ahajournals.org/doi/abs/10.1161/HYPERTENSIONAHA.125.26091","authors":["Mehmet Kanbay"],"significance":5,"published":"2026-03-19","source_date":"2026-03-19","image":"","kennis":["https://hartvaat.nl/kennis/farmacologie/aldosteron-en-raas-farmacologie/","https://hartvaat.nl/kennis/hypertensie/hypertensie-en-ckd/"],"congress":"","summary_en":"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.","created":"2026-07-03T10:32:22Z","updated":"2026-07-03T18:39:23Z","licence":"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.","body_markdown":"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.","abstract_original":"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."}