The differences in brain stem transcriptional profiling in hypertensive ISIAH and normotensive WAG rats
| Autor: | Leonid O. Klimov, Olga E. Redina, L. A. Fedoseeva, Yuriy L. Orlov, Nikita I. Ershov, Arcady L. Markel, V. M. Efimov |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0106 biological sciences
medicine.medical_specialty Candidate gene Transcriptional profiling lcsh:QH426-470 lcsh:Biotechnology Central nervous system Blood Pressure Biology Baroreflex Essential hypertension 01 natural sciences Brain stem 03 medical and health sciences chemistry.chemical_compound Species Specificity Stress Physiological Internal medicine lcsh:TP248.13-248.65 Genetics medicine Animals Stress-sensitive hypertension RNA-Seq ISIAH rat strain 030304 developmental biology 0303 health sciences Aldosterone Adrenal gland Research Gene Expression Profiling Molecular Sequence Annotation medicine.disease Rats lcsh:Genetics medicine.anatomical_structure Blood pressure Endocrinology chemistry Hypertension Homeostasis Transcription Factors 010606 plant biology & botany Biotechnology |
| Zdroj: | BMC Genomics, Vol 20, Iss S3, Pp 1-16 (2019) BMC Genomics |
| ISSN: | 1471-2164 |
| Popis: | Background The development of essential hypertension is associated with a wide range of mechanisms. The brain stem neurons are essential for the homeostatic regulation of arterial pressure as they control baroreflex and sympathetic nerve activity. The ISIAH (Inherited Stress Induced Arterial Hypertension) rats reproduce the human stress-sensitive hypertensive disease with predominant activation of the neuroendocrine hypothalamic-pituitary-adrenal and sympathetic adrenal axes. RNA-Seq analysis of the brain stems from the hypertensive ISIAH and normotensive control WAG (Wistar Albino Glaxo) rats was performed to identify the differentially expressed genes (DEGs) and the main central mechanisms (biological processes and metabolic pathways) contributing to the hypertensive state in the ISIAH rats. Results The study revealed 224 DEGs. Their annotation in databases showed that 22 of them were associated with hypertension and blood pressure (BP) regulation, and 61 DEGs were associated with central nervous system diseases. In accordance with the functional annotation of DEGs, the key role of hormonal metabolic processes and, in particular, the enhanced biosynthesis of aldosterone in the brain stem of ISIAH rats was proposed. Multiple DEGs associated with several Gene Ontology (GO) terms essentially related to modulation of BP were identified. Abundant groups of DEGs were related to GO terms associated with responses to different stimuli including response to organic (hormonal) substance, to external stimulus, and to stress. Several DEGs making the most contribution to the inter-strain differences were detected including the Ephx2, which was earlier defined as a major candidate gene in the studies of transcriptional profiles in different tissues/organs (hypothalamus, adrenal gland and kidney) of ISIAH rats. Conclusions The results of the study showed that inter-strain differences in ISIAH and WAG brain stem functioning might be a result of the imbalance in processes leading to the pathology development and those, exerting the compensatory effects. The data obtained in this study are useful for a better understanding of the genetic mechanisms underlying the complexity of the brain stem processes in ISIAH rats, which are a model of stress-sensitive form of hypertension. Electronic supplementary material The online version of this article (10.1186/s12864-019-5540-5) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|