{"id":"46086","type":"article","url":"https://hartvaat.nl/2026/04/09/grootschalige-proteomics-van-bloeddruk-en-hypertensie-wijst-nherf2-aan-als-mogel/","title":"Grootschalige proteomics van bloeddruk en hypertensie wijst NHERF2 aan als mogelijk doelwit","title_en":"Integrative Proteomic Profiling of Blood Pressure and Hypertension","category":"hypertensie","category_label":"Hypertensie","professions":["cardioloog","huisarts","internist"],"tags":[],"journal":"Hypertension","doi":"https://www.ahajournals.org/doi/abs/10.1161/HYPERTENSIONAHA.125.26407","source_url":"https://doi.org/https://www.ahajournals.org/doi/abs/10.1161/HYPERTENSIONAHA.125.26407","authors":["Mohit Aggarwal"],"significance":7,"published":"2026-07-23","source_date":"2026-04-09","image":"","kennis":["https://hartvaat.nl/kennis/hypertensie/hypertensie-en-ckd/","https://hartvaat.nl/kennis/hypertensie/eindorgaanschade-hypertensie/"],"congress":"","summary_en":"Hypertension affects one-third of adults worldwide and is largely idiopathic; protein biomarkers may reveal underlying mechanisms and treatment targets. This study linked 2,922 plasma proteins to blood pressure (systolic and diastolic) and hypertension in 45,991 UK Biobank participants, validated in 5,759 Framingham Heart Study participants. In the UK Biobank, 342 proteins were associated with systolic and 276 with diastolic blood pressure; new-onset hypertension was associated with 60 proteins. Mendelian randomisation identified hundreds of proteins with a causal signal, involved in blood-vessel and cardiac-muscle morphogenesis, vasoconstriction and inflammation; BP-related proteins were enriched for atherosclerotic, liver and kidney diseases. NHERF2 emerged as a putatively causal protein and promising therapeutic target. The study thus provides a comprehensive protein signature of blood pressure and hypertension risk.","created":"2026-07-03T20:27:17Z","updated":"2026-07-04T19:26:48Z","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 treft wereldwijd een derde van de volwassenen en is grotendeels idiopathisch; eiwitbiomarkers kunnen onderliggende mechanismen en behandelaanknopingspunten blootleggen. In deze studie werden 2.922 plasma-eiwitten gekoppeld aan bloeddruk (systolisch en diastolisch) en hypertensie bij 45.991 UK Biobank-deelnemers, met validatie in 5.759 deelnemers van de Framingham Heart Study. In de UK Biobank waren 342 eiwitten geassocieerd met de systolische en 276 met de diastolische bloeddruk; nieuw ontstane hypertensie hing samen met 60 eiwitten. Mendeliaanse randomisatie wees honderden eiwitten met een causaal signaal aan, betrokken bij bloedvat- en hartspiermorfogenese, vasoconstrictie en ontsteking; de bloeddrukgerelateerde eiwitten waren verrijkt voor atherosclerotische, lever- en nierziekten. NHERF2 kwam naar voren als een mogelijk causaal eiwit en veelbelovend therapeutisch doelwit. De studie levert zo een uitgebreide eiwithandtekening van bloeddruk en hypertensierisico.","abstract_original":"Hypertension, Volume 83, Issue 6, Page e26407, June 1, 2026. BACKGROUND:Hypertension affects one-third of adults worldwide and is largely idiopathic. Identifying protein biomarkers of hypertension may reveal underlying mechanisms and potential treatments.METHODS:We examined associations between 2922 plasma proteins and blood pressure (BP) traits (systolic BP [SBP] and diastolic BP [DBP], and prevalent hypertension) in 45 991 UK Biobank participants with validation in 5759 FHS (Framingham Heart Study) participants. Analysis of new-onset hypertension was performed in 3995 UK Biobank participants and validated in 3073 FHS participants. Functional enrichment analysis linked proteins to biological functions and diseases. Mendelian randomization assessed causal relations between proteins usingcis-protein quantitative trait loci as exposures and BP traits as outcomes.RESULTS:In the UK Biobank, 342 proteins were associated (false discovery rate knockoff <0.1) with SBP, 276 with DBP, and 200 with prevalent hypertension (N=24 724). In the FHS, 115 proteins were validated (Bonferroni-correctedP<0.05) for SBP, 108 for DBP, and 102 for hypertension. New-onset hypertension was associated with 60 (17 validated) proteins. Mendelian randomization analyses revealed significant associations for 206, 210, and 82 proteins with SBP, DBP, and hypertension, respectively. Several of these proteins are involved in blood vessel and cardiac muscle morphogenesis, vasoconstriction, and inflammation. BP-related proteins are enriched for atherosclerotic cardiovascular, liver, and kidney diseases. NHERF2 (Na+/H+exchange regulatory cofactor 2) demonstrated putatively causal associations with SBP, DBP, and with prevalent and new-onset hypertension.CONCLUSIONS:This large-scale proteomic study revealed protein signatures of BP traits and hypertension risk, highlighting inflammation and cardiac and vascular remodeling processes; NHERF2 and several other proteins emerged as promising therapeutic targets."}