Histoenzymological analysis of the development of myocardial metabolic heterogeneity in the rat ontogenesis

Authors

DOI:

https://doi.org/10.26641/1997-9665.2025.2.59-65

Keywords:

myocardium, ontogenesis, rats, metabolism, systole, diastole, enzyme histochemistry.

Abstract

Relevance. Topological and chronological features in the implementation of leading reactions of energy metabolism in cardiomyocytes, mechanisms of interaction between different metabolic cycles at the stages of ontogenetic development, as well as the formation of a clear metabolic heterogeneity of cardiomyocytes have not yet been fully explained. The aim of this study was to histochemically determine ontogenetic changes in the activity of key enzymes of cardiomyocyte energy metabolism in different localizations of the rat heart in systole and diastole. Methods. Histoenzymological determination of the activity of phosphofructokinase, lactate dehydrogenase, succinate dehydrogenase, isocitrate dehydrogenase, glucose-6-phosphate dehydrogenase in cryostat sections of the myocardium of the ventricles, atria and septa of the rat heart in systole and diastole starting from the 14th day of the prenatal period to puberty was carried out. Results and conclusion. Typical cardiomyocytes of mature rat myocardium are in three different metabolic statuses. In the first status, their sarcoplasm has a low intensity of glycolysis in diastole and a high intensity in systole against the background of a stably active tricarboxylic acid cycle and low activity of pentose phosphate reactions in both phases of cardiac contraction. In the second status, typical cardiomyocytes have low activity of glycolysis, pentose phosphate shunt, and tricarboxylic acid cycle in systole and diastole. In the third status, which is characteristic of singly located cardiac myocytes, a high intensity of the tricarboxylic acid cycle and low activity of glycolytic and pentose phosphate reactions are observed regardless of the phase of cardiac contraction. The formation of metabolic heterogeneity of typical cardiomyocytes during cardiogenesis is based on the limitation of anaerobic glycolytic reactions and the intensification of oxidative phosphorylation. The rates of energy transformations are most active in the intramural and subepicardial zones of both ventricles, the least active in the atria and interatrial septum.

References

  1. Tsedeke AT, Allanki S, Gentile A, Jimenez-Amilburu V, Rasouli SJ, Guenther S, Lai SL, Stainier DYR, Marín-Juez R. Cardiomyocyte heterogeneity during zebrafish development and regeneration. Dev Biol. 2021;476:259-71. doi: 10.1016/j.ydbio.2021.03.014.
  2. Sedmera D, McQuinn T. Embryogenesis of the heart muscle. Heart Fail Clin. 2008 Jul;4(3):235-45. doi: 10.1016/j.hfc.2008.02.007.
  3. Obata K, Morita H, Takaki M. The energy-saving effect of a new myosin activator, omecamtiv mecarbil, on LV mechanoenergetics in rat hearts with blood-perfused isovolumic contraction model. Naunyn Schmiedebergs Arch Pharmacol. 2019;392(9):1065-70. doi: 10.1007/s00210-019-01685-4.
  4. Han JC, Pham T, Taberner AJ, Loiselle DS, Tran K. Resolving an inconsistency in the estimation of the energy for excitation of cardiac muscle contraction. Front Physiol. 2023;14:1269900. doi: 10.3389/fphys.2023.1269900.
  5. Lopaschuk GD, Jaswal JS. Energy metabolic phenotype of the cardiomyocyte during development, differentiation, and postnatal maturation. J Cardiovasc Pharmacol. 2010;56(2):130-40. doi: 10.1097/FJC.0b013e3181e74a14.
  6. Martin-Puig S, Menendez-Montes I. Cardiac Metabolism. Adv Exp Med Biol. 2024;1441:365-96. doi: 10.1007/978-3-031-44087-8_19.
  7. Cui M, Wang Z, Bassel-Duby R, Olson EN. Genetic and epigenetic regulation of cardiomyocytes in development, regeneration and disease. Development. 2018;145(24):dev171983. doi: 10.1242/ dev.171983.
  8. Cheng YY, Gregorich Z, Prajnamitra RP, Lundy DJ, Ma TY, Huang YH, Lee YC, Ruan SC, Lin JH, Lin PJ, Kuo CW, Chen P, Yan YT, Tian R, Kamp TJ, Hsieh PCH. Metabolic changes associated with cardiomyocyte dedifferentiation enable adult mammalian cardiac regeneration. Circulation. 2022;146(25):1950-67. doi: 10.1161/CIRCULATIONAHA.122.061960.
  9. Huang L, Wang Q, Gu S, Cao N. Integrated metabolic and epigenetic mechanisms in cardiomyocyte proliferation. J Mol Cell Cardiol. 2023;181:79-88. doi: 10.1016/j.yjmcc.2023.06.002.
  10. Mullins PD, Bondarenko VE. Mathematical model for β1-adrenergic regulation of the mouse ventricular myocyte contraction. Am J Physiol Heart Circ Physiol. 2020;318(2):H264-H282. doi: 10.1152/ajpheart.00492.2019.
  11. Piquereau J, Ventura-Clapier R. Maturation of cardiac energy metabolism during perinatal development. Front Physiol. 2018;9:959. doi: 10.3389/fphys.2018.00959.
  12. Chong D, Gu Y, Zhang T, Xu Y, Bu D, Chen Z, Xu N, Li L, Zhu X, Wang H, Li Y, Zheng F, Wang D, Li P, Xu L, Hu Z, Li C. Neonatal ketone body elevation regulates postnatal heart development by promoting cardiomyocyte mitochondrial maturation and metabolic reprogramming. Cell Discov. 2022;8(1):106. doi: 10.1038/s41421-022-00447-6.
  13. Alan L, Opletalova B, Hayat H, Markovic A, Hlavackova M, Vrbacky M, Mracek T, Alanova P. Mitochondrial metabolism and hypoxic signaling in differentiated human cardiomyocyte AC16 cell line. Am J Physiol Cell Physiol. 2025;328(5):C1571-85. doi: 10.1152/ajpcell.00083.2025.
  14. Cianflone E, Scalise M, Marino F, Salerno L, Salerno N, Urbanek K, Torella D. The negative regulation of gene expression by microRNAs as key driver of inducers and repressors of cardiomyocyte differentiation. Clin Sci (Lond). 2022;136(16):1179-203. doi: 10.1042/CS20220391.
  15. Chen X, Wu H, Liu Y, Liu L, Houser SR, Wang WE. Metabolic reprogramming: a byproduct or a driver of cardiomyocyte proliferation? Circulation. 2024;149(20):1598-610. doi: 10.1161/CIRCULATIONAHA.123.065880.
  16. Kraus L. Targeting epigenetic regulation of cardiomyocytes through development for therapeutic cardiac regeneration after heart failure. Int J Mol Sci. 2022;23(19):11878. doi: 10.3390/ijms231911878.
  17. Zeng C, Wu J, Li J. Pyruvate Kinase M2: A potential regulator of cardiac injury through glycolytic and non-glycolytic pathways. J Cardiovasc Pharmacol. 2024;84(1):1-9. doi: 10.1097/FJC.0000000000001568.
  18. Jacobs RE, Fraser KE. Magnetic resonance microscopy of embryonic cell lineages and movements. Science. 1994;263:681–4.
  19. Suvarna SK, Layton C, Bancroft GD. (Eds.). Bancroft's Theory and Practice of Histological Techniques, 8th Edition. Elsevier; 2019. 558 p. https://doi.org/10.1016/B978-0-7020-6864-5.00008-6
  20. European Convention for the protection of vertebrate animals used for experimental and other scientific purposes. Strasburg: Council of Europe. 1986;123:52.
  21. Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the Protection of Animals Used for Scientific Purposes. Off J Eur Union. 2010;53(L276):33–79.

Downloads

Published

2025-07-30

How to Cite

Chelpanova , I. (2025). Histoenzymological analysis of the development of myocardial metabolic heterogeneity in the rat ontogenesis. Морфологія / Morphologia / Morfologìâ, 19(2), 59–65. https://doi.org/10.26641/1997-9665.2025.2.59-65

Issue

Vol. 19 No. 2 (2025)

Section

Статті

License

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

 The authors reserve the right to authorship of their work and transfer to the Journal the right to the first publication of this work under the terms of a license Creative commons Attribution 4.0 International (CC BY 4.0), which allows other people to freely distribute the published work with a mandatory reference to the authors of the original work and the first publication of the work in this journal.
        By submitting a manuscript to the editorial office of the Journal ‘Morphologia’ authors agree to transfer the rights to protect and use the manuscript (all supplemental materials, particularly protected objects such as photos, drawings, diagrams, tables, etc.), including the reproduction in the press and distribution via the Internet; translation of the manuscript into any language; export and import of journal copies with the Authors’ article in order to make it available for public. Authors convey the rights mentioned above to the editorial office without any temporal or territorial limitation all over the world. 
        The Authors guarantee that they have the exclusive rights to use the material transferred to editorial office. Editors are not responsible to third parties for contraventions of warranty given by the Authors. The considered rights are transferred to the editorial office since the moment when the current issue is signed for publishing. Reproduction of materials published in the Journal by other individuals and legal entities is possible only with the consent of Editorial office, with the obligatory indication of the full bibliographic reference of the primary publication. The Authors reserve the right to use the published material, its fragments and parts for teaching materials, oral presentations, dissertation thesis prepararion with obligatory bibliographic citation of the original paper. Electron copy of the published article, downloaded from official journal web-site in .pdf format may be put by authors on the official web-site of their institutions, any other official resources with open access.