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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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>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\u2010PCR, regression analysis, phenome\u2010wide association study and case\u2013control analysis of a missense polymorphism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>We identified 60 genes that were significantly differentially expressed in hypertensive monocytes, many of which are related to IL\u20101\u03b2. Uni\u2010 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\u201018 receptor accessory protein (IL18RAP) remained significantly elevated in peripheral monocytes of hypertensive individuals in a separate validation cohort. Interestingly, IL18RAP expression associated with MAP in a cohort of African Americans. Furthermore, homozygosity for a missense single nucleotide polymorphism in LTF that decreases antimicrobial function and increases protein levels (rs1126478) was over\u2010represented in patients with hypertension relative to controls (odds ratio 1.16).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>These data demonstrate that monocytes exhibit enhanced pro\u2010inflammatory gene expression in hypertensive individuals and identify IL18RAP and LTF as potential novel mediators of human hypertension.<\/jats:p><\/jats:sec><jats:sec><jats:title>Linked Articles<\/jats:title><jats:p>This article is part of a themed section on Immune Targets in Hypertension. To view the other articles in this section visit <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v176.12\/issuetoc\">http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v176.12\/issuetoc<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.14364","type":"journal-article","created":{"date-parts":[[2018,5,18]],"date-time":"2018-05-18T07:49:50Z","timestamp":1526629790000},"page":"2015-2027","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Human monocyte transcriptional profiling identifies IL\u201018 receptor accessory protein and lactoferrin as novel immune targets in hypertension"],"prefix":"10.1111","volume":"176","author":[{"given":"Matthew R","family":"Alexander","sequence":"first","affiliation":[{"name":"Division of Cardiovascular Medicine Vanderbilt University Medical Center  Nashville TN 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