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高血压ISIAH大鼠下丘脑去甲肾上腺素浓度和心脏质量与18号染色体上的一个基因座相关。

Hypothalamic Norepinephrine Concentration and Heart Mass in Hypertensive ISIAH Rats Are Associated with a Genetic Locus on Chromosome 18.

作者信息

Redina Olga E, Smolenskaya Svetlana E, Polityko Yulia K, Ershov Nikita I, Gilinsky Michael A, Markel Arcady L

机构信息

Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 10 Lavrentieva Ave., 630090 Novosibirsk, Russia.

Scientific Research Institute of Physiology and Basic Medicine, 4 Timakova Street, 630117 Novosibirsk, Russia.

出版信息

J Pers Med. 2021 Jan 23;11(2):67. doi: 10.3390/jpm11020067.

Abstract

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. The work describes a genetic locus on chromosome 18, in which there are genes that control the development of cardiac hypertrophy associated with an increase in the concentration of norepinephrine in the hypothalamus, i.e., genes involved in enhanced sympathetic myocardial stimulation. No association of this locus with the blood pressure was found. Taking into consideration previously obtained results, it was concluded that the contribution to the development of heart hypertrophy in the ISIAH rats is controlled by different genetic loci, one of which is associated with the concentration of norepinephrine in the hypothalamus (on chromosome 18) and the other is associated with high blood pressure (on chromosome 1). Nucleotide substitutions that may be involved in the formation or absence of association with blood pressure in different rat strains are discussed.

摘要

交感神经系统激活与心脏肥大之间的关系早已为人所知。然而,这种关联的分子遗传学基础却知之甚少。鉴于下丘脑去甲肾上腺素在交感神经系统激活中的已知作用,该研究的目的是使用数量性状基因座(QTL)分析进行基因定位,并确定与下丘脑去甲肾上腺素浓度升高以及模拟应激敏感性动脉高血压形式的遗传性应激诱导性动脉高血压(ISIAH)大鼠心脏质量增加相关的基因座。该研究描述了18号染色体上的一个基因座,其中存在控制与下丘脑去甲肾上腺素浓度升高相关的心脏肥大发展的基因,即参与增强交感神经对心肌刺激的基因。未发现该基因座与血压有关联。考虑到先前获得的结果,得出的结论是,ISIAH大鼠心脏肥大发展的贡献由不同的基因座控制,其中一个与下丘脑去甲肾上腺素浓度有关(位于18号染色体上),另一个与高血压有关(位于1号染色体上)。讨论了可能参与不同大鼠品系中与血压关联形成或缺失的核苷酸替换。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32fc/7911892/222274559ce2/jpm-11-00067-g001.jpg

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