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Renal Transcriptome Analysis of Programmed Hypertension Induced by Maternal Nutritional Insults.

ABSTRACT: Maternal nutrition can affect development, leading to long-term effects on the health of offspring. The most common outcome is programmed hypertension. We examined whether alterations in renal transcriptome are responsible for generating programmed hypertension among four different models using next-generation RNA sequencing (NGS) technology. Pregnant Sprague-Dawley rats received 50% caloric restriction (CR), intraperitoneal injection of 45 mg/kg streptozotocin, 60% high-fructose (HF) diet, or 1% NaCl in drinking water to conduct CR, diabetes, HF, or high-salt models, respectively. All four models induced programmed hypertension in adult male offspring. We observed 16 shared genes in a two-week-old kidney among four different models. The identified differential expressed genes (DEGs) that are related to the regulation of blood pressure included Adrb3, Alb, Apoe, Calca, Kng1, Adm2, Guca2b, Hba2, Hba-a2, and Ppara. The peroxisome proliferator-activated receptor (PPAR) signaling pathway and glutathione metabolism pathway were shared by the CR, diabetes, and HF models. Conclusively, a variety of maternal nutritional insults induced the same phenotype-programmed hypertension with differential alterations of renal transcriptome in adult male offspring. The roles of DEGs identified by the NGS in this study deserve further clarification to develop ideal maternal dietary interventions and thus spare the next generations from the burden of hypertension.

SUBMITTER: Tain YL

PROVIDER: S-EPMC4581224 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Renal Transcriptome Analysis of Programmed Hypertension Induced by Maternal Nutritional Insults.

Tain You-Lin YL Hsu Chien-Ning CN Chan Julie Y H JY Huang Li-Tung LT

International journal of molecular sciences 20150803 8

Maternal nutrition can affect development, leading to long-term effects on the health of offspring. The most common outcome is programmed hypertension. We examined whether alterations in renal transcriptome are responsible for generating programmed hypertension among four different models using next-generation RNA sequencing (NGS) technology. Pregnant Sprague-Dawley rats received 50% caloric restriction (CR), intraperitoneal injection of 45 mg/kg streptozotocin, 60% high-fructose (HF) diet, or 1 ...[more]

PMID: 26247937

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Project description:UNLABELLED:Key points summary Maternal high-fructose (HF) induces programmed hypertension in adult offspring.Early aliskiren administration prevents HF-induced hypertension in both sexes of adult offspring.HF regulates RAS components in the offspring kidney in a sex-specific manner.HF alters renal transcriptome, with female offspring being more sensitive.Deprogramming strategy to prevent hypertension might be sex-specific. BACKGROUND:Maternal high fructose (HF) intake induced renal programming and hypertension in male adult offspring. We examined whether maternal HF intake causes programmed hypertension and whether aliskiren administration confers protection against the process in a sex-specific manner, with a focus on the transcriptome changes in the kidney using next-generation RNA sequencing (NGS) technology and renin-angiotensin system (RAS). METHODS:Pregnant Sprague-Dawley rats received regular chow or chow supplemented with 60% fructose throughout pregnancy and lactation. Offspring were assigned to six groups: male control, male HF (MHF), MHF+Aliskiren, female control, female HF (FHF), and FHF+Aliskiren. Oral aliskiren 10 mg/kg/day was administered via gastric gavage between 2 and 4 weeks of age. Rats were sacrificed at 12 weeks of age. RESULTS:Maternal HF intake induced programmed hypertension in 12-week-old offspring of both sexes. HF regulated renal transcriptome and RAS components in the offspring kidney in a sex-specific manner. Aliskiren administration prevented HF-induced programmed hypertension in both sexes of adult offspring. Aliskiren administration increased ACE2 and MAS protein levels in female kidneys exposed to maternal HF intake. CONCLUSION:Maternal HF induced programmed hypertension in both sexes of adult offspring, which was sex-specifically mitigated by early aliskiren administration. Better understanding of the sex-dependent mechanisms that underlie maternal HF-induced renal programming will help develop a novel sex-specific strategy to prevent programmed hypertension.

Project description:BackgroundThe hypothalamus has an important role in the onset and maintenance of hypertension and stress responses. Rats with inherited stress-induced arterial hypertension (ISIAH), reproducing the human stress-sensitive hypertensive state with predominant involvement of the neuroendocrine hypothalamic-pituitary-adrenal and sympathoadrenal axes, were used for analysis of the hypothalamus transcriptome.ResultsRNA-seq analysis revealed 139 genes differentially expressed in the hypothalami of hypertensive ISIAH and normotensive Wistar Albino Glaxo (WAG) rats. According to the annotation in databases, 18 of the differentially expressed genes (DEGs) were associated with arterial hypertension. The Gene Ontology (GO) functional annotation showed that these genes were related to different biological processes that may contribute to the hypertension development in the ISIAH rats. The most significantly affected processes were the following: regulation of hormone levels, immune system process, regulation of response to stimulus, blood circulation, response to stress, response to hormone stimulus, transport, metabolic processes, and endocrine system development. The most significantly affected metabolic pathways were those associated with the function of the immune system and cell adhesion molecules and the metabolism of retinol and arachidonic acid. Of the top 40 DEGs making the greatest contribution to the interstrain differences, there were 3 genes (Ephx2, Cst3 and Ltbp2) associated with hypertension that were considered to be suitable for further studies as potential targets for the stress-sensitive hypertension therapy. Seven DEGs were found to be common between hypothalamic transcriptomes of ISIAH rats and Schlager mice with established neurogenic hypertension.ConclusionsThe results of this study revealed multiple DEGs and possible mechanisms specifying the hypothalamic function in the hypertensive ISIAH rats. These results provide a basis for further investigation of the signalling mechanisms that affect hypothalamic output related to stress-sensitive hypertension development.

Project description:Background: Breviscapine (Dengzhanhua) injection has been wildly used in clinical treatment for cerebral infarction, cardiovascular disease, diabetic nephropathy, renal impairment of essential hypertension and stroke in China. Breviscapine injection and antihypertensive drugs combination therapy is supposed to be beneficial for hypertension-induced renal damage patients. Objectives: To evaluate the beneficial and adverse effects of breviscapine injection on hypertension in hypertension-induced renal damage patients, an extensive meta-analysis was performed. Methods: We searched PubMed, the Cochrane Library, Embase, CNKI, Sino Med, VIP, and Wanfang Data for relevant literature. The timeframe of retrieval was set from the founding date of each database to September 28, 2018. Results: Fourteen papers were included in this study. The quality of all the studies included was determined to be low. All studies were conducted with Chinese populations. Meta-analysis showed that, compared with single-use antihypertensive drugs, using breviscapine injection in combination with antihypertensive drugs to treat hypertension in hypertension-induced renal damage patients can reduce 24-h urinary total protein (24 h UTP) [WMD = -0.04, 95% CI (-0.05, -0.02), P ? 0.001], but does not lower systolic blood pressure (SBP) [WMD = -1.02, 95% CI (-2.88, 0.84), P = 0.281] or diastolic blood pressure (DBP) [WMD = -0.21, 95% CI (-1.71, 1.29), P = 0.786] more effectively. There was also no statistically significant difference in adverse events between experimental groups and control groups. Conclusion: Breviscapine injection, in combination with antihypertensive drugs, appears to be more effective in improving the 24 h UTP, but overall have no effect on improving the blood pressure in hypertension-induced renal damage patients. Moderate dose of breviscapine injection (10 ml) may have effects on reducing blood pressure in hypertension-induced renal damage patients but high doses of breviscapine injection (20 ml) may increase blood pressure by subgroup analysis. However, the evidence of methodological quality and sample sizes is weak, and thus, further standardized research is required.

Dataset Information

Renal Transcriptome Analysis of Programmed Hypertension Induced by Maternal Nutritional Insults.

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Renal Transcriptome Analysis of Programmed Hypertension Induced by Maternal Nutritional Insults.

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