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应激、基因与高血压。ISIAH 大鼠品系研究的贡献。

Stress, Genes, and Hypertension. Contribution of the ISIAH Rat Strain Study.

机构信息

Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 10 Lavrentieva ave., Novosibirsk, Russia, 630090.

Novosibirsk State University, Novosibirsk, Russian Federation.

出版信息

Curr Hypertens Rep. 2018 Jun 16;20(8):66. doi: 10.1007/s11906-018-0870-2.

Abstract

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.

RECENT FINDINGS

Recent findings helped to characterize the main neuroendocrine mechanisms and the specificity of the genetic background contributing to the stress-sensitive hypertension development in the ISIAH rats. The ISIAH rat strain, which is an original model of the stress-sensitive arterial hypertension, can be considered as "living" proof that the genetic predisposition to increased stress-reactivity can lead to the development of persistent stress-dependent arterial hypertension. The ISIAH rat strain is characterized by the genetically determined enhanced response of the neuroendocrine and renal regulatory systems to stress and is a suitable model that allows one to explore the genetic and physiological mechanisms involved in stress-sensitive hypertension development. There are common genetic loci (QTLs) associated with both basal and stress-induced blood pressure (BP) levels as well as QTLs associated with BP and other traits, which may be related to hypertension development in ISIAH rats. Multiple genes differentially expressed in the target organs/tissues of hypertensive ISIAH and normotensive control rats are associated with many biological processes and metabolic pathways involved in stress response and arterial hypertension. The genotype of ISIAH rats is characterized by numerous specific and common SNPs as compared with other models of hypertensive rats. The results of the studies are valuable for the search for genetic markers specific for stress-induced arterial hypertension, as well as for the selection of new molecular targets that may be potentially useful for prevention and/or therapy of hypertensive disease.

摘要

综述目的

急性精神情绪应激是血压急剧升高的原因之一。然而,应激是否会促进高血压病的发展仍是一个悬而未决的问题。本综述旨在:首先,表明遗传决定的对压力的增强反应与持续高血压的发展有关;其次,阐明应激敏感型高血压发病机制中涉及的主要生理机制和遗传因素。

最新发现

最近的发现有助于描述主要的神经内分泌机制和遗传背景的特异性,这些机制和遗传背景有助于 ISIAH 大鼠应激敏感型高血压的发展。ISIAH 大鼠是应激敏感型动脉高血压的原始模型,它可以被认为是“活体”证据,证明遗传倾向于增强应激反应性可能导致持续的应激依赖性动脉高血压的发展。ISIAH 大鼠的特点是遗传决定的神经内分泌和肾脏调节系统对压力的反应增强,是一种合适的模型,可以用来探索应激敏感型高血压发展中涉及的遗传和生理机制。存在与基础和应激诱导的血压(BP)水平相关的共同遗传位点(QTL)以及与 BP 和其他特征相关的 QTL,这些 QTL 可能与 ISIAH 大鼠的高血压发展有关。在高血压 ISIAH 大鼠和正常血压对照大鼠的靶器官/组织中差异表达的多个基因与许多涉及应激反应和动脉高血压的生物学过程和代谢途径有关。与其他高血压大鼠模型相比,ISIAH 大鼠的基因型具有许多特异性和共同的 SNP。这些研究结果对于寻找应激诱导的动脉高血压特异性遗传标记物以及选择可能对高血压病的预防和/或治疗有用的新分子靶点具有重要价值。

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