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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Genet. | doi: 10.3389/fgene.2018.00684

Time- and ventricular-specific expression profiles of genes encoding Z-disk proteins in pressure overload model of left ventricular hypertrophy

 Anastasia Knyazeva1*, Alexander Krutikov1,  Alexey Golovkin1, Alexander Mishanin1, Georgii Pavlov2, Natalia Smolina1, 3, Thomas Sejersen4, Gunnar Sjoberg4, Mikhail Galagoudza1 and  Anna Kostareva1, 3, 4
  • 1Almazov National Medical Research Centre, Russia
  • 2Saint Petersburg State Academy of Veterinary Medicine, Russia
  • 3ITMO University, Russia
  • 4Karolinska Institute (KI), Sweden

Mechanotransduction is an essential mechanism of transforming external mechanical stimulis to biochemical response. In cardiomyocytes mechanotransduction plays an important role in contraction, stretch sensing and homeostasis regulation. One of the major mechanosensitive area in cardiomyocytes, the Z-disk, consists of numbers of structural and signaling proteins, that may undergo conformational or gene expression changes under pathological stress conditions. In present study we examined a rat model of pressure overload cardiac hypertrophy validated by echocardiographic and histopathological examinations. We revealed, that during hypertrophy progression expression of several genes encoding Z-disk proteins (Actn2, Ldb3, Cmya5, Nebl) is different at early and late points of cardiac remodeling. Moreover, expression patterns of several genes are opposite in myocardium of overloaded left ventricle and hemodynamically unaffected right ventricle, and expression profiles in interventricular septum are more similar to right ventricle. Additionally, we revealed inconsistencies between mRNA and protein level changes of Actn, one of the major structural Z-disk element. All these findings point out, that investigated Z-disk proteins participate in pathological stress adaptation through undergoing the gene expression changes, and suggest the novel important role of hypertrophic response modulation during different stages of cardiac remodeling.

Keywords: cardiac hypertrophy, Z-disk, mechanotranduction, Pressure overload, sarcomere

Received: 03 Oct 2018; Accepted: 07 Dec 2018.

Edited by:

M. Z. A. Bhuiyan, Lausanne University Hospital (CHUV), Switzerland

Reviewed by:

Boris Shenkman, Institute of Biomedical Problems (RAS), Russia
Andreas Brodehl, Heart and Diabetes Center North Rhine-Westphalia, Germany  

Copyright: © 2018 Knyazeva, Krutikov, Golovkin, Mishanin, Pavlov, Smolina, Sejersen, Sjoberg, Galagoudza and Kostareva. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Ms. Anastasia Knyazeva, Almazov National Medical Research Centre, Saint Petersburg, Russia, knyazeva.aa26@gmail.com