Human monocyte transcriptional profiling identifies IL-18 receptor accessory protein and lactoferrin as novel immune targets in hypertension

British Journal of Pharmacology
Matthew R AlexanderMeena S Madhur

Abstract

Monocytes play a critical role in hypertension. The purpose of our study was to use an unbiased approach to determine whether hypertensive individuals on conventional therapy exhibit an altered monocyte gene expression profile and to perform validation studies of selected genes to identify novel therapeutic targets for hypertension. Next generation RNA sequencing identified differentially expressed genes in a small discovery cohort of normotensive and hypertensive individuals. Several of these genes were further investigated for association with hypertension in multiple validation cohorts using qRT-PCR, regression analysis, phenome-wide association study and case-control analysis of a missense polymorphism. We identified 60 genes that were significantly differentially expressed in hypertensive monocytes, many of which are related to IL-1β. Uni- and multivariate regression analyses of the expression of these genes with mean arterial pressure (MAP) revealed four genes that significantly correlated with MAP in normotensive and/or hypertensive individuals. Of these, lactoferrin (LTF), peptidoglycan recognition protein 1 and IL-18 receptor accessory protein (IL18RAP) remained significantly elevated in peripheral monocytes of hyperte...Continue Reading

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Citations

Aug 6, 2019·Journal of the Renin-angiotensin-aldosterone System : JRAAS·Krzysztof PlesińskiMaria Szczepańska
May 28, 2019·British Journal of Pharmacology·Antony VinhChristopher G Sobey
Feb 23, 2020·Hypertension·Meena S MadhurDavid G Harrison
Jan 27, 2021·International Journal of Molecular Sciences·Carmen De MiguelSantiago Cuevas
Oct 11, 2020·Blood Pressure Monitoring·Ertuğrul Emre GüntürkMustafa Topuz
Apr 2, 2021·Circulation Research·Meena S MadhurAnnet Kirabo
Mar 25, 2021·Journal of Cardiovascular Pharmacology·Yanxin HanWei Jin

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