Pathogenetic features of morphodensitometric characteristics of cardiomyocytes and marker profile of the left ventricular remodeling in rats with experimental intermittent hypoxia of different duration

Yu. M. Kolesnyk, M. I. Isachenko



Myocardial remodeling is considered as a three-component complex process, including cardiomyocyte hypertrophy, their apoptosis, interstitial and perivascular fibrosis. At the same time, the nature of remodeling and the direction of restructuring in the myocardium depend on the prevalence of one of these processes, the degree of their severity and the impact duration. Therefore, to understand the effect of short- and long-term intermittent hypoxia on the direction of myocardial remodeling and its type, the aim of this study was to determine the pathogenetic features of the morphodensitometric characteristics of cardiomyocytes and the marker profile of left ventricular myocardial remodeling in the rats with experimental intermittent hypoxia durated 15 and 60 days.

Material and methods. A total of 30 male Wistar rats aging 6-10 months were used for the experiment and assigned to 3 experimental groups of 10 animals each: control; rats exposed to 15-day hypoxia; rats exposed to 60-day hypoxia. The object of the study was the left ventricular myocardium. The number of nuclei in an image, their average linear size and density (the ratio of the total area of nuclei to the area of the cytoplasm), and the concentration of RNA in the nucleus and cytoplasm were measured in the sections stained by Einarson via morphodensitometric method. An immunofluorescence method was used to study the content of immunoreactive material to markers of remodeling (cardiotrophin-1, type I collagen, titin, annexin V). As a result of the study, it was found that intermittent hypoxia led to a decrease in the number of nuclei in cardiomyocytes in both experimental groups compared to the control. Such changes in the number of nuclei were accompanied by significantly larger nuclear size compared to the control (in rats with 15-day hypoxia by 52.9 %, in rats with 60-day hypoxia - by 153.4 %) and a decrease in the density of nuclei in relation to the cytoplasm by 19.5 % and 21.2 %, respectively. In both groups, a significantly lower control concentration of RNA in the nuclei of cardiomyocytes was found alongside with an increase in their area. Such changes were accompanied by a significantly higher concentration of RNA by 23.2 % in the cytoplasm in case of long-term intermittent hypoxia. The marker profile of remodeling parameters in rats exposed to 15-day hypoxia was characterized by a higher content of cardiotrophin-1 and titin by 11.5 % and 23.1 %, respectively, as compared to the control. The content of type I collagen was 19.9 % higher, while the content of annexin V did not change significantly. In rats with long-term 60-day hypoxia, the content of cardiotrophin-1 was higher by 73.6 %, titin - by 124.9 %, type I collagen - by 41.9 %, and annexin V - by 95.9 % in comparison to the control. When calculating the titin / collagen ratio in rats based on their content, a significant increase in myocardial stiffness was determined in the 60-day hypoxia group which was 1.44, while it was0.91 in the control, and in rats with 15-day short-term hypoxia – 0.93.

Conclusions. Intermittent hypoxic effects, regardless of duration, result in morpho-structural rearrangements of the myocardium, are characterized by an increase in viscoelastic mechanical properties and the development of hypertrophy, but with an increase in the duration of exposure (60 days) – by an additional formation of interstitial fibrosis and apoptosis of cardiomyocytes. Short-term hypoxia forms a hypertrophic type of myocardial remodeling with a decrease in the number of nuclei alongside with an increase in their size and a moderate decrease in RNA concentration. The marker profile of remodeling changes in a physiological manner and is characterized by an increase in the content of cardiotrophin-1, type I collagen and titin, while maintaining the titin / collagen ratio and normal apoptotic rate. Long-term hypoxia causes a fibro-apoptotic type of pathological myocardial remodeling including an almost two-fold decrease in the number of nuclei with an increase in their size and a decrease in RNA concentration. The marker profile of remodeling is characterized by an increase in all 4 components, a significant increase in the titin / collagen ratio and high apoptotic rate of cardiomyocytes.


titin, annexin V; cardiotrophin-1; type I collagen; myocardium; left ventricle of the heart; intermittent hypoxia; Wistar rats

Full Text:



Yalçin, F., Kucukler, N., Cingolani, O., Mbiyangandu, B., Sorensen, L., Pinherio, A., Abraham, M. R., & Abraham, T. P. (2019). Evolution of ventricular hypertrophy and myocardial mechanics in physiological and pathological hypertrophy. Journal of applied physiology (Bethesda, Md. : 1985), 126(2), 354–362.

Tham, Y. K., Huynh, K., Mellett, N. A., Henstridge, D. C., Kiriazis, H., Ooi, J., Matsumoto, A., Patterson, N. L., Sadoshima, J., Meikle, P. J., & McMullen, J. R. (2018). Distinct lipidomic profiles in models of physiological and pathological cardiac remodeling, and potential therapeutic strategies. Biochimica et biophysica acta. Molecular and cell biology of lipids, 1863(3), 219–234.

Kolesnyk, Yu.M., Kolesnyk, M.I., Abramov, A.V., Tumanskyi, V.O., Hancheva, O.V. (2015) Imunohistokhimichna i morfo-densytometrychna diahnostyka patolohichnoho remodeliuvannia miokarda pry arterialnoi hipertenzii ta tsukrovomu diabeti (Metodychni rekomendatsii). Kyiv, 25s. (Ukrainian).

Shimizu, I., & Minamino, T. (2016). Physiological and pathological cardiac hypertrophy. Journal of molecular and cellular cardiology, 97, 245–262.

Hong, J., Chu, M., Qian, L., Wang, J., Guo, Y., & Xu, D. (2017). Fibrillar Type I Collagen Enhances the Differentiation and Proliferation of Myofibroblasts by Lowering α2β1 Integrin Expression in Cardiac Fibrosis. BioMed research international, 2017, 1790808.

Ding, Y., Wang, Y., Jia, Q., Wang, X., Lu, Y., Zhang, A., Lv, S., & Zhang, J. (2020). Morphological and Functional Characteristics of Animal Models of Myocardial Fibrosis Induced by Pressure Overload. International journal of hypertension, 2020, 3014693.

Galluzzi, L., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Agostinis, P., Alnemri, E. S., Altucci, L., Amelio, I., Andrews, D. W., Annicchiarico-Petruzzelli, M., Antonov, A. V., Arama, E., Baehrecke, E. H., Barlev, N. A., Bazan, N. G., Bernassola, F., Bertrand, M., Bianchi, K., Blagosklonny, M. V., Kroemer, G. (2018). Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018. Cell death and differentiation, 25(3), 486–541.

Zakon Ukrainy № 3447-IV «Pro zakhyst tvaryn vid zhorstkoho povodzhennia». Vidomosti Verkhovnoi Rady Ukrainy.2006;№ 27:s230. (Ukrainian).

Kolesnyk, Yu.M., Hancheva, O.V., Abramov, A.V., Ivanenko, T.V., Fedotova, M.I., Danukalo, M.V., (2016) inventors; Zaporizhzhia State Medical University, assignee. Method of modeling physiological myocardial remodeling in small rodents. Ukraina pat. 112290. Dec 12. (Ukrainian).

Kolesnyk, Y., Isachenko, M., & Melnikova, O. (2019). The features of the nitric oxide system in the left ventricle myocardium in the rats with experimental intermittent hypoxia of different duration. Pathologia, 0(3). doi: 10.14739/2310-1237.2019.3.188783.

Fedotova, M.I., Kovalov, M.M., Zhulinskyi, V.O., Kadzharian, Ye.V. (2017) Osoblyvosti ekspresii izoform syntazy oksydu azotu u miokardi livoho shlunochka shchuriv pry arterialnii hipertenzii riznoho henezu. Aktualni problemy suchasnoi medytsyny: Visnyk Ukrainskoi medychnoi stomatolohichnoi akademii.;17,4(60): 91−95. (Ukrainian).

Zaitsev VM, Lyfliandskyi VH, Marynkyn VY. (2006) Prykladnaia medytsynskaia statystyka. Sankt-Peterburh:Folyant.432 s.(Russian).

Corno, A. F., Milano, G., Morel, S., Tozzi, P., Genton, C. Y., Samaja, M., & von Segesser, L. K. (2004). Hypoxia: unique myocardial morphology?. The Journal of thoracic and cardiovascular surgery, 127(5), 1301–1308.

Zhong, Z., Hu, J. Q., Wu, X. D., Sun, Y., & Jiang, J. (2016). Anti-apoptotic effects of myocardin-related transcription factor-A on rat cardiomyocytes following hypoxia-induced injury. Canadian journal of physiology and pharmacology, 94(4), 379–387.

Mirtschink, P., & Krek, W. (2016). Hypoxia-driven glycolytic and fructolytic metabolic programs: Pivotal to hypertrophic heart disease. Biochimica et biophysica acta, 1863(7 Pt B), 1822–1828.

Sataeva, T. P., & Zadnipryany, I. V. (2018). Issledovanie markerov remodelirovaniia miokarda pri éksperimental'noĭ gipobaricheskoĭ gipoksii na fone korrektsii preparatom tsitoflavin [Investigation of markers for myocardial remodeling during experimental hypobaric hypoxia in the correction with cytoflavin]. Arkhiv patologii, 80(6), 35–42. (Russian).

Koser, F., Loescher, C., & Linke, W. A. (2019). Posttranslational modifications of titin from cardiac muscle: how, where, and what for?. The FEBS journal, 286(12), 2240–2260.

de Jong, R., Pluijmert, N. J., de Vries, M. R., Pettersson, K., Atsma, D. E., Jukema, J. W., & Quax, P. (2018). Annexin A5 reduces infarct size and improves cardiac function after myocardial ischemia-reperfusion injury by suppression of the cardiac inflammatory response. Scientific reports, 8(1), 6753.

Article Metrics

Metrics Loading ...

Metrics powered by PLOS ALM

Journal of Education, Health and Sport formerly Journal of Health Sciences

Declaration on the original version.

Editors indicates that the main version of the magazine is to issue a "electronic".

The journal has had 5 points in Ministry of Science and Higher Education parametric evaluation. § 8. 2) and § 12. 1. 2) 22.02.2019.

1223 Journal of Education, Health and Sport eISSN 2391-8306 7

ISSN 2391-8306 formerly ISSN: 1429-9623 / 2300-665X

Archives 2011 - 2014

PBN 2011 - 2014

POL-index 2011 - 2014

BASE 2011 - 2014

Indexed in Bases, Bazy indeksacyjne: ERIH Plus, Worldcat, PBN/POL-Index, ICI Journals Master List, Directory of Open Access Journals (DOAJ), ZBD, Ulrich's periodicals, Google Scholar, Polska Bibliografia Lekarska, EuroPub database, NLM Catalog Result - NCBI, BASE, Russian Sciences Index, Arianta.

US NLM = 101679844

101679844 - NLM Catalog Result - NCBI

Find a library that holds this journal:


PBN Poland



Redaction, Publisher and Editorial Office

Publisher and Editorial Office
Department of Physical Culture,
Faculty of Earth Sciences and Spatial Management,
Nicolaus Copernicus University in Toruń, Poland
Address: Str. Lwowska 1, 87-100 Toruń, Poland

  Open Access ISSN 2391-8306 formerly ISSN: 1429-9623 / 2300-665X

The journal has been approved for inclusion in ERIH PLUS.

The ERIH PLUS listing of the journal is available at

Indexed in Index Copernicus Journals Master List.,p24782242,3.html

ICV 2019 = 100.00 ICV 2018 = 95.95 ICV 2017 = 91.30 ICV 2016 = 84.69 ICV 2015 = 93.34 ICV 2014 = 89.51 Standardized Value: 8.27 ICV 2013: 7.32 ICV 2012: 6.41 ICV 20115.48

RG Journal Impact: 0.18 *

*This value is calculated using ResearchGate data and is based on average citation counts from work published in this journal. The data used in the calculation may not be exhaustive.

RG Journal impact history

2020Available summer 2021
2018 / 20190.18

RG Journal impact over time

RG Journal impact

Indexed in Polish Scholarly Bibliography (PBN) (PBN Polska Bibliografia Naukowa) (

is a portal of the Polish Ministry of Science and Higher Education, collecting information on publications of Polish scientists and on Polish and foreign scholarly journals. Polish Scholarly Bibliograhpy is a part of POL-on - System of Information on Higher Education. It is operated by the Interdisciplinary Centre for Mathematical and Computational Modelling, University of Warsaw.

Indexed in Russian Sciences Index Российский индекс научного цитирования (РИНЦ)

Indexed in Arianta Polish scientific and professional electronic journals Aneta Drabek i Arkadiusz Pulikowski


Partnerzy platformy czasopism