Publications by authors named "Arcady Markel"

Normotensive and hypertensive organisms respond differently to stress factors; however, the features of the central molecular genetic mechanisms underlying the reaction of the hypertensive organism to stress have not been fully established. In this study, we examined the transcriptome profiles of the hypothalamus of hypertensive ISIAH rats, modeling a stress-sensitive form of arterial hypertension, and normotensive WAG rats at rest and after exposure to a single short-term restraint stress. It was shown that oxidative phosphorylation is the most significantly enriched process among metabolic changes in the hypothalamus of rats of both strains when exposed to a single short-term restraint stress.

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Emotional stress is one of the health risk factors in the modern human lifestyle. Stress exposure can provoke the manifestation of various pathological conditions, one of which is a sharp increase in the blood pressure level. In the present study, we analyzed changes in the transcriptome profiles of the hypothalamus of hypertensive ISIAH and normotensive WAG rats exposed to a single short-term restraint stress (the rat was placed in a tight wire-mesh cage for 2 h).

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The process of domestication, despite its short duration as it compared with the time scale of the natural evolutionary process, has caused rapid and substantial changes in the phenotype of domestic animal species. Nonetheless, the genetic mechanisms underlying these changes remain poorly understood. The present study deals with an analysis of the transcriptomes from four brain regions of gray rats (), serving as an experimental model object of domestication.

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Research into genetic and physiological mechanisms of widespread disorders such as arterial hypertension as well as neuropsychiatric and other human diseases is urgently needed in academic and practical medicine and in the field of biology. Nevertheless, such studies have many limitations and pose difficulties that can be overcome by using animal models. To date, for the purposes of creating animal models of human pathologies, several approaches have been used: pharmacological/chemical intervention; surgical procedures; genetic technologies for creating transgenic animals, knockouts, or knockdowns; and breeding.

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Hypertension is one of the most significant risk factors for many cardiovascular diseases. At different stages of hypertension development, various pathophysiological processes can play a key role in the manifestation of the hypertensive phenotype and of comorbid conditions. Accordingly, it is thought that when diagnosing and choosing a strategy for treating hypertension, it is necessary to take into account age, the stage of disorder development, comorbidities, and effects of emotional-psychosocial factors.

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Article Synopsis
  • The study investigates how gene expressions linked to age-related diseases (ARDs) vary among different genders, ages, and disease types to improve personalized medicine approaches.
  • Researchers sequenced the transcriptome of two types of rats—tame and aggressive—to find behavior-related gene expressions and compared them to known ARD-linked genes.
  • The analysis revealed a significant correlation between the gene expressions related to behavior and ARD susceptibility, identifying a key molecular marker: an excess of Fcγ receptor IIb, which suppresses immune hyperactivation.
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Article Synopsis
  • Studies on the genetic basis of tame behavior during animal domestication highlight their relevance in both basic and applied research, especially in understanding behavior in domesticated species like gray rats.
  • Researchers used high-throughput RNA sequencing to compare gene expression in the midbrains of tame versus aggressive rats, identifying 42 differentially expressed genes associated with behavior, including three transcription factors (TFs) that play significant roles.
  • The expression of the TF gene Ascl3 in tame rats suggests a link to longer neurogenesis and neoteny, positioning ASCL3 as a key factor influencing behavioral changes during domestication.
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Long noncoding RNAs (lncRNAs) play an important role in the control of many physiological and pathophysiological processes, including the development of hypertension and other cardiovascular diseases. Nonetheless, the understanding of the regulatory function of many lncRNAs is still incomplete. This work is a continuation of our earlier study on the sequencing of hypothalamic transcriptomes of hypertensive ISIAH rats and control normotensive WAG rats.

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Article Synopsis
  • Hypertension often runs in families, but genetic research shows that known genetic factors only account for a small part of its heredity, prompting the need for more personalized treatment approaches.
  • The study aimed to identify universal genetic markers for hypertension by analyzing gene expression in the brains of rats with different stress levels, linking stress reaction to hypertension risk.
  • Findings revealed two potential biomarkers—β-protocadherins and hemoglobin—that are downregulated in hypertensive patients and could be used in broader hypertension management strategies.
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Belyaev's concept of destabilizing selection during domestication was a major achievement in the XX century. Its practical value has been realized in commercial colors of the domesticated fox that never occur in the wild and has been confirmed in a wide variety of pet breeds. Many human disease models involving animals allow to test drugs before human testing.

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The relationship between activation of the sympathetic nervous system and cardiac hypertrophy has long been known. However, the molecular genetic basis of this association is poorly understood. Given the known role of hypothalamic norepinephrine in the activation of the sympathetic nervous system, the aim of the work was to carry out genetic mapping using Quantitative Trait Loci (QTL) analysis and determine the loci associated both with an increase in the concentration of norepinephrine in the hypothalamus and with an increase in heart mass in Inherited Stress-Induced Arterial Hypertension (ISIAH) rats simulating the stress-sensitive form of arterial hypertension.

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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.

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Background: Fat mass and obesity-associated (FTO) gene has been under close investigation since the discovery of its high impact on the obesity status in 2007 by a range of publications. Recent report on its implication in adipocytes underscored its molecular and functional mechanics in pathology. Still, the population specific features of the locus structure have not been approached in detail.

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Purpose Of Review: Acute psychoemotional stress is one of the causes of a sharp increase in blood pressure. However, the question if the stress may promote the hypertensive disease development is still open. This review aims, firstly, to show that the genetically determined enhanced responsiveness to stress is linked to sustained hypertension development and, secondly, to characterize the main physiological mechanisms and genetic factors implicated in the pathogenesis of stress-sensitive hypertension.

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The presented data contains information about component composition of lipophilic compounds in fungal body sample obtained using gas chromatography and subsequent mass spectrometry.

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Background: As the standard clinically used hypotensive medicines have many undesirable side effects, there is a need for new therapeutic agents, especially ones of a natural origin.

Purpose: One possible candidate is extract from the mushroom Reishi (Ganoderma lucidum), which is used in the treatment and prevention of many chronic diseases.

Study Design And Methods: To study the effectiveness of Reishi, which grows in the Altai Mountains, as an antihypertensive agent, we intragastrically administered Reishi water extract to adult male hypertensive ISIAH (inherited stress-induced arterial hypertension) rats.

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Background: The changes in the renal function leading to a reduction of medullary blood flow can have a great impact on sodium and water homeostasis and on the long-term control of arterial blood pressure. The RNA-Seq approach was used for transcriptome profiling of the renal medulla from hypertensive ISIAH and normotensive WAG rats to uncover the genetic basis of the changes underlying the renal medulla function in the ISIAH rats being a model of the stress-sensitive arterial hypertension and to reveal the genes which possibly may contribute to the alterations in medullary blood flow.

Results: Multiple DEGs specifying the function of renal medulla in ISIAH rats were revealed.

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Background: The adrenals are known as an important link in pathogenesis of arterial hypertensive disease. The study was directed to the adrenal transcriptome analysis in ISIAH rats with stress-sensitive arterial hypertension and predominant involvement in pathogenesis of the hypothalamic-pituitary-adrenal and sympathoadrenal systems.

Results: The RNA-Seq approach was used to perform the comparative adrenal transcriptome profiling in hypertensive ISIAH and normotensive WAG rats.

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Objective: Association between stress and hypertensive disease is still a matter of debate. Can stress be the cause of hypertensive disease and, if so, what mechanisms are involved? To clarify this question, the Inherited stress-induced arterial hypertensive rat strain (ISIAH rat strain) with a stress related arterial hypertension was developed by selection for the enhanced blood pressure response to 0.5 h restraint stress.

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Article Synopsis
  • The study focuses on the hypothalamus' role in hypertension and stress, using rats with inherited stress-induced arterial hypertension (ISIAH) as a model.
  • RNA sequencing identified 139 differentially expressed genes (DEGs) in ISIAH rats compared to normotensive rats, with 18 DEGs linked to arterial hypertension.
  • Key biological processes and metabolic pathways associated with these DEGs include hormone regulation, immune response, and stress, highlighting potential therapeutic targets for managing stress-sensitive hypertension.
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Background: The renal function plays a leading role in long-term control of arterial pressure. The comparative analysis of renal cortex transcriptome in ISIAH rats with inherited stress-induced arterial hypertension and normotensive WAG rats was performed using RNA-Seq approach. The goal of the study was to identify the differentially expressed genes (DEGs) related to hypertension and to detect the pathways contributing to the differences in renal functions in ISIAH and WAG rats.

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Background: The kidney mass is significantly increased in hypertensive ISIAH rats with Inherited Stress Induced Arterial Hypertension as compared with normotensive WAG rats. The QTL/microarray approach was carried out to determine the positional candidate genes in the QTL for absolute and relative kidney weight.

Results: Several known and predicted genes differentially expressed in ISIAH and WAG kidney were mapped to genetic loci associated with the absolute and relative kidney weight in 6-month old F2 hybrid (ISIAHxWAG) males.

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Remote ischemic preconditioning (RIPC) is a recent trend in cardiovascular medicine. From the literature, it may be deduced that physiological changes resulted from repeated episodes of brachial-cuff inflation/deflation during RIPC provoke, in some way, systemic "training" of the whole organism. At the same time, the effectiveness of such a "training" is substantially different in different humans, and the latter remains unclear.

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Transcriptional activity of the kidney genes was compared in hypertensive ISIAH and normotensive WAG rats using the oligonucleotide microarray technique. Most of differentially expressed genes were downregulated in ISIAH kidney both in renal cortex and medulla. According to functional annotation the kidney function in ISIAH rats is based on altered expression of many genes working in stress-related mode.

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