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Gender differences in the cytokines and chemokines gene expression profiles within the medulla oblongata of SHRs

ABSTRACT: Medulla oblongata is a region of the brain containing multiple blood pressure regulation centers, including the nucleus of the solitary tract (NTS), a pivotal region for regulating the set-point of arterial pressure. Our previous findings suggest that the NTS of male pre-hypertensive rats and spontaneously hypertensive rats (SHRs) exhibits abnormal inflammatory condition compared with that of normotensive Wistar-Kyoto (WKY) rats. Females of SHRs exhibit a lower blood pressure than their male counterpart but the molecular mechanism is not well described. To unveil the gender differences in the central regulation of blood pressure, we investigated the gene expression profile of cytokines and chemokines in the medulla oblongata of female SHRs compared to that of their male counterparts.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE87746 | GEO | 2016/10/12

SECONDARY ACCESSION(S): PRJNA347856

REPOSITORIES: GEO

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Project description:Abstract Background: Long-term hypertension can lead to hypertensive heart disease, which ultimately progresses to heart failure. As an angiotensin receptor blocker (ARB) antihypertensive drug, allisartan can control blood pressure and improve cardiac remodeling and cardiac dysfunction caused by hypertension. The objective of this study is to investigate the protective effects of Allisartan on the heart of spontaneously hypertensive rats (SHRs) and the underlying mechanisms. Methods: We used spontaneously hypertensive rats (SHRs) as an animal model of hypertensive heart disease and treated them with allisartan orally at a dose of 25 mg/(Kg·day). We continuously monitored the rats' blood pressure levels, measured their body and heart weights, and evaluated their cardiac structure and function using echocardiography. WGA staining and Masson trichrome staining were employed to assess the morphology of the myocardial tissue. We performed transcriptome and proteome analysis using the Solexa/Illumina sequencing platform and tandem mass tag (TMT) technology, respectively. We used immunofluorescence co-localization to analyze Nrf2 nuclear translocation, and TUNEL to detect the level of cell apoptosis. The protein and mRNA levels were determined by Western blotting and qRT-PCR, respectively. Results: Allisartan lowered blood pressure, attenuated cardiac remodeling, and improved cardiac function. Allisartan alleviated cardiomyocyte hypertrophy and cardiac fibrosis. Allisartan significantly affected the pentose phosphate pathway, fatty acid elongation, valine, leucine and isoleucine degradation, glutathione metabolism, and amino sugar and nucleotide sugar metabolism pathways in the hearts of SHRs, and upregulated the expression level of GSTM2. Allisartan activated the PI3K-AKT-Nrf2 signaling pathway and inhibited cardiomyocyte apoptosis. Conclusions: Our study determined that allisartan effectively controls blood pressure in SHRs and improves cardiac remodeling and cardiac dysfunction. Allisartan upregulates the expression level of GSTM2 in the hearts of SHRs and significantly affects glutathione metabolism shown by transcriptomics and proteomics analysis. The cardioprotective effect of allisartan may be mediated through activation of the PI3K-AKT-Nrf2 signaling pathway, upregulation of GSTM2 expression, and reduction of SHRs cardiomyocyte apoptosis.

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Gender differences in the cytokines and chemokines gene expression profiles within the medulla oblongata of SHRs

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