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Identification of Inflammatory Biomarkers for Hypertension from Isolated Human Monocytes
Author(s) -
Norlander Allison Elizabeth,
Galindo Cristi L,
Elijovich Fernando,
Laffer Cheryl L,
Montaniel Kim Ramil Contreras,
Gnecco Juan S,
Madhur Meena S
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1079.1
Subject(s) - medicine , blood pressure , inflammation , kidney disease , myocardial infarction , cohort , mean arterial pressure , disease , kidney , monocyte , candidate gene , gene , endocrinology , biology , genetics , heart rate
Individuals on traditional hypertensive treatments are still more likely to develop cardiovascular and kidney complications, including occurrences of myocardial infarction and chronic kidney disease, than normotensive individuals. In recent years, our laboratory has demonstrated a role for inflammation, while specifically characterizing the contribution of monocytes and dendritic cells, in the development of hypertension. We embarked on the current study in attempts to determine, through an unbiased approach, if individuals on conventional hypertensive therapies have altered monocytic gene expression compared to normotensive humans that could help to explain the maintenance of increased cardiovascular risk. We used next generation RNA sequencing to profile monocytes isolated from the peripheral blood of 5 normotensive and 7 hypertensive subjects. We identified 60 transcripts that were significantly differentially expressed. Regression analysis was performed on these transcripts in order to correlate them with mean arterial pressure (MAP). After multivariate analyses, two genes, LTF (r=0.99, p<0.0001) and PGLYRP1 (r=0.99, p<0.005) significantly correlated with MAP in normotensive individuals. GZMH (r=0.88, p<0.01) significantly correlated with MAP in hypertensive individuals. While, IL18RAP significantly correlated with MAP in normotensive (r=0.93, p<0.03) and hypertensive (r=0.78, p<0.04) humans. Finally, we examined transcript expression of the four genes identified in the regression analyses in combination with several other candidate genes identified as significantly differentially expressed in the original analysis using quantitative RT‐PCR in a separate cohort of 6 normotensive and 9 hypertensive subjects. We were able to validate 6 out of 8 transcripts tested; expression of LTF (3.13 fold, p=0.0128), MMP8 (3.78 fold, p=0.044), ARG1 (1.39 fold, p=0.0248), PGLYRP1 (4.62 fold, p=0.0332), and IL18RAP (2.1 fold, p=0.038) all significantly increased in hypertensives while expression of VSIG4 (1.7 fold, p=0.0248) significantly decreased in hypertensives. These data demonstrate that monocytes from treated hypertensive patients exhibit a pro‐inflammatory gene signature which could potentially serve as biomarkers for disease severity and may explain the residual cardiovascular risk in these individuals. Support or Funding Information NIH T32 Training Grant; F31 Predoctoral Individual National Research Service Award; AHA Strategically Focused Prevention Research Network Grant; NIH NHLBI K08 Award