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The differences in brain stem transcriptional profiling in hypertensive ISIAH and normotensive WAG rats. / Fedoseeva, Larisa A.; Klimov, Leonid O.; Ershov, Nikita I. et al.
In: BMC Genomics, Vol. 20, No. Suppl 3, 297, 08.05.2019.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - The differences in brain stem transcriptional profiling in hypertensive ISIAH and normotensive WAG rats
AU - Fedoseeva, Larisa A.
AU - Klimov, Leonid O.
AU - Ershov, Nikita I.
AU - Efimov, Vadim M.
AU - Markel, Arcady L.
AU - Orlov, Yuriy L.
AU - Redina, Olga E.
PY - 2019/5/8
Y1 - 2019/5/8
N2 - 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.
AB - 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.
KW - Brain stem
KW - ISIAH rat strain
KW - RNA-Seq
KW - Stress-sensitive hypertension
KW - Transcriptional profiling
KW - BLOOD-PRESSURE REGULATION
KW - SOLUBLE EPOXIDE HYDROLASE
KW - GENE
KW - RNA-SEQ
KW - ARTERIAL-HYPERTENSION
KW - THERAPEUTIC TARGET
KW - SYMPATHETIC-NERVE ACTIVITY
KW - STRESS
KW - INHIBITOR
KW - ISCHEMIC-STROKE
UR - http://www.scopus.com/inward/record.url?scp=85065441047&partnerID=8YFLogxK
U2 - 10.1186/s12864-019-5540-5
DO - 10.1186/s12864-019-5540-5
M3 - Article
C2 - 32039698
AN - SCOPUS:85065441047
VL - 20
JO - BMC Genomics
JF - BMC Genomics
SN - 1471-2164
IS - Suppl 3
M1 - 297
ER -
ID: 20043516