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This article is part of the Research Topic

The Role of Hypoxia in the Regulation of Metabolism

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

Front. Endocrinol. | doi: 10.3389/fendo.2018.00809

Cardioprotective regimen of adaptation to chronic hypoxia diversely alters myocardial gene expression in SHR and SHR-mtBN conplastic rat strains

 Iveta Nedvedova1, David Kolar1,  Jan Neckar2, Martin Kalous3, Michal Pravenec4, Jan Silhavy4, Korenkova Vlasta4, Frantisek Kolar2 and  Jitka M. Zurmanova1, 5*
  • 1Department of Physiology, Faculty of Science, Charles University, Czechia
  • 2Institute of Physiology (ASCR), Czechia
  • 3Department of Cell Biology, Faculty of Science, Charles University, Czechia
  • 4Institute of Biotechnology, Czech Academy of Sciences,, Czechia
  • 5Charles University, Czechia

Adaptation to continuous normobaric hypoxia (CNH) protects the heart against acute ischemia/reperfusion injury. Recently, we have demonstrated the infarct size-limiting effect of CNH also in hearts of spontaneously hypertensive rats (SHR) and in conplastic SHR-mtBN strain characterized by the selective replacement of the mitochondrial genome of SHR with that of more ischemia-resistant Brown Norway rats. Importantly, cardioprotective effect of CNH was more pronounced in SHR-mtBN than in SHR. Thus, here we aimed to identify candidate genes which may contribute to this difference between the strains. Rats were adapted to CNH (FiO2 0.1) for 3 weeks or kept at room air as normoxic controls. Screening of 45 transcripts was performed in left ventricles using Biomark Chip. Significant differences between the groups were analyzed by univariate analysis (ANOVA) and the genes contributing to the differences between the strains unmasked by CNH were identified by multivariate analyses (PCA, SOM). ANOVA with Bonferroni correction revealed that transcripts differently affected by CNH in SHR and SHR-mtBN belong predominantly to lipid metabolism and antioxidant defence. PCA divided four experimental groups into two main clusters corresponding to chronically hypoxic and normoxic groups, and differences between the strains were more pronounced after CNH. Subsequently, the following 14 candidate transcripts were selected by PCA, and confirmed by SOM analyses, that can contribute to the strain differences in cardioprotective phenotype afforded by CNH: Alkaline ceramidase 2 (Acer2), Fatty acid translocase (Cd36), Aconitase 1 (Aco1), Peroxisome proliferator activated receptor gamma (Pparg), Hemoxygenase 2 (Hmox2), Phospholipase A2 group IIA (Ppla2g2a), Dynamin-related protein (Drp), Protein kinase C epsilon (Pkce) Hexokinase 2 (Hk2), Sphingomyelin synthase 2 (Sgms2), Caspase 3 (Casp3), Mitofussin 1 (Mfn1), Phospholipase A2 group V (Pla2g5) and Catalase (Cat). Our data suggests that the stronger cardioprotective phenotype of conplastic SHR-mtBN strain afforded by CNH is associated with either preventing the drop or increasing the expression of transcripts related to energy metabolism, antioxidant response and mitochondrial dynamics.

Keywords: SHR (spontaneous hypertensive rat), conplastic strain; SHR-mtBN, Left ventricle, hypoxia, Metabolism

Received: 25 Jul 2018; Accepted: 24 Dec 2018.

Edited by:

Slava Berger, Johns Hopkins Medicine, United States

Reviewed by:

Zhichao Feng, Albert Einstein College of Medicine, United States
Luciano Drager, Heart Institute, Clinical Hospital, Faculty of Medicine, University of São Paulo, Brazil  

Copyright: © 2018 Nedvedova, Kolar, Neckar, Kalous, Pravenec, Silhavy, Vlasta, Kolar and Zurmanova. 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: PhD. Jitka M. Zurmanova, Charles University, Prague, Czechia,