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Articles

Altered expression of norepinephrine transporter participate in hypertension and depression through regulated TNF-α and IL-6

, , , &
Pages 181-189 | Received 18 Oct 2018, Accepted 07 Mar 2019, Published online: 07 Apr 2019
 

ABSTRACT

Aim: We explored the role of histone modification in the association of depression-hypertension by comparing norepinephrine transporter (NET) gene levels in different depression-hypertensive patients. Then, we analyzed the expression of NET correlation with inflammatory cytokines to provide a new direction for detecting the association mechanism between depression and hypertension.

Methods: NE expression levels in serum of diverse groups were detected by enzyme-linked immunosorbent assay. Then histone acetyltransferase (HAT), histone deacetylase (HDAC), H3K27ac, NET, TNF-α, and interleukin-6 (IL-6) were detected by western blot in nine female subjects in different depression and hypertension groups, and Chromatin immunoprecipitation-polymerase chain reaction (Chip-PCR) were used to confirm the degree of acetylation affecting on the transcription level of NET gene. Meanwhile, correlation between NET with TNF/IL-6 was analyzed by SPSS19.0 software program. Finally, Quantitative real-time polymerase chain reaction (qPCR) and western blot were used to detect TNF-α and IL-6 expression levels after NET overexpression or interference treatment in human umbilical vein endothelial cells and Neuro-2a cells.

Results: The expression of HAT and H3K27ac had lower levels in D-H and nonD-H group than nonD-nonH group. The results showed that higher acetylation could promote expression of NET genes. Meanwhile, the expression of NET had a significant negative correlation with IL-6 (R = −0.933, p < 0.01) and tumor necrosis factor (TNF) (R = −0.817, p < 0.01) in subjects. In addition, the results confirmed that TNF-α and IL-6 mRNA and protein partial expressions could be inhibited by NET in both HUVECs and Neuronal cells (p < 0.01).

Conclusion: In conclusion, differential expression of NET gene might function as an important factor in interaction between depression and hypertension by partially targeting TNF-α and IL-6.

Acknowledgments

This work was supported by the grant from the National Natural Science Foundation of China (Grant No: 81400310).

Disclosure Statement

The authors declare no conflict of interest.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [81400310].

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