Abstract 19446: Effect of Changing Sodium Intake on miRNA Profiling in Hypertensives
Introduction: High sodium intake is an important risk factor for hypertension and CVD. However, the basic underlying mechanisms are not well understood. Animal studies demonstrate that miRNAs play a role in high sodium intake-induced myocardial fibrosis and salt-sensitive hypertension.
Hypothesis: We aim to test the hypothesis that high sodium intake induced changes in circulating miRNA expression in hypertensives.
Methods: A whole genome miRNA next generation sequencing was performed in paired serum samples (pre and post slow release sodium tablets) selected from 10 black male untreated hypertensive subjects (aged 43 to 68 years) in a randomized double-blind crossover trial (slow release sodium vs placebo while on low-sodium diet). Samples were sequenced on the Illumina NextSeq 500 system. The differential expression analysis was done using the EdgeR statistical software package. Benjamini-Hochberg FDR was used to adjust for multiple comparisons. mirTarBase (version 6.0) was used to identify miRNA target genes.
Results: On average 10.2 million reads were obtained per sample. miR-425-3p (1.55 folds), miR-4433-3p (1.80 folds) and miR-4433-5p (1.54 folds) were significantly upregulated with an increase in sodium intake (raw ps<0.05, FDR>0.80). miR-143-3p (0.71 folds), miR-223-5p (0.76 fold) and miR-148a-3p (0.82 folds) were significantly downregulated (raw ps<0.05, FDR>0.80). miR-425-3p was involved in cell death. miR-143-3p was previously associated with apoptosis, and pulmonary arterial hypertension. miR-223-5p has been involved in obesity, sepsis-induced inflammation (IL6 and TNFα), myocardial dysfunction and mortality in the literature. miR-148a-3p is a novel repressor of IKBKB, NF-κB signaling and inflammation. In our study, 118 genes were associated with the 3 upregulated miRNAs and 601 genes were associated with the 3 downregulated miRNAs. GO enrichment analysis showed that upregulated miRNA associated genes were enriched in regulation of transcription and cell cycle. Downregulated miRNA associated genes were enriched in regulation of cell proliferation.
Conclusions: A change in sodium intake affects miRNA expression, which could be one of the underlying mechanisms that high sodium intake promotes hypertension and CVD.
Author Disclosures: H. Zhu: None. F. He: None. J. Choi: None. Y. Dong: None. Y. Huang: None. G.A. Harshfield: None.
- © 2016 by American Heart Association, Inc.