Retrospective analysis of the morphofunctional architectonics and pathohistological transformation of the myocardium: from the molecular norm to regenerative potential in remodelling and ischaemia (literature review)

Authors

DOI:

https://doi.org/10.26641/1997-9665.2026.2.5-11

Keywords:

myocardium, histological architecture, ischemia, myocardial infarction, immunohistochemistry.

Abstract

Introduction. Myocardial viability depends on the spatial organization of subcellular structures (ion clusters, nanodomains), whose disorganization of which causes rhythm disturbances even before the appearance of histological signs of necrosis. This makes an in-depth study of cardiac microarchitecture critically important for clinical practice. Aim. To systematize modern histological, ultrastructural, and immunohistochemical criteria for evaluating the myocardium in normal conditions, during adaptive remodeling, ischemia, and inflammation, as well as to analyze the regenerative potential of the tissues. Methods. A systematic review was conducted, resulting in the selection of 25 sources from the PubMed, Scopus, and Web of Science databases spanning 1990–2026 (with a focus on the last 5 years) using the keywords: myocardium, histology, pathology. Results. Normal myocardial architecture is maintained by intercalated discs and ankyrins, which serve as molecular "anchors" for ion channels. During hypoxia, ankyrin proteolysis disrupts this stability. In ischemia, ultrastructural changes (mitochondrial swelling) are recorded as early as 30 minutes. For the ultra-early verification of true ischemia and necrosis, specific immunohistochemical markers (C9 complex, SIRT1) are utilized, and the local tissue loss of troponin C is monitored. Post-necrotic remodeling culminates in irreversible collagen scarring involving myofibroblasts (α-SMA expression). Surviving muscle "bridges" within the scar can generate arrhythmias. Simultaneously, regeneration faces the connexin-43 (Cx43) paradox: although differentiated progenitor cells express it, the excessive extracellular matrix physically isolates cardiomyocytes, blocking electrical contacts. Conclusion. The early verification of ischemia and inflammation relies on electron microscopy and specific markers (C9, CD3). Overcoming barriers in regenerative medicine requires comprehensive histomatrix analysis to combat fibrosis and restore conduction.

References

  1. Litviňuková M, Talavera-López C, Maatz H, Reichart D, Worth CL, Lindberg EL, et al. Cells of the adult human heart. Nature. 2020;588:466-72. doi: 10.1038/s41586-020-2797-4.
  2. Federspiel JM, Schmidt PH, Corvest E, Hohneck JE, Meier C. Cardiac dissection techniques for pathoanatomical research on myocardial hypertrophy and anatomical teaching. Ann Anat. 2025;262:152711. doi: 10.1016/j.aanat.2025.152711.
  3. Jensen B, Petersen SE, Coolen BF. Myocardial perfusion in excessively trabeculated hearts: Insights from imaging and histological studies. J Cardiol. 2023;81(6):499-507. doi: 10.1016/j.jjcc.2022. 11.013.
  4. Mescher A. Junqueira's basic histology: text and atlas. 17th ed. New York: McGraw Hill; 2023.
  5. Basso C, Aguilera B, Banner J, Cohle S, d’Amati G, de Gouveia RH, et al. Guidelines for autopsy investigation of sudden cardiac death: 2017 update from the Association for European Cardiovascular Pathology. Virchows Arch. 2017;471:691-705. doi: 10.1007/s00428-017-2221-0.
  6. Stone JR, Basso C, Baandrup UT, Bruneval P, Butany J, Gallagher PJ, et al. Recommendations for processing cardiovascular surgical pathology specimens: a consensus statement from the Standards and Definitions Committee of the Society for Cardiovascular Pathology and the Association for European Cardiovascular Pathology. Cardiovasc Pathol. 2012;21:2-16. doi: 10.1016/j.carpath.2011.01.001.
  7. Wilson AJ, Sands GB, LeGrice IJ, Young AA, Ennis DB. Myocardial mesostructure and mesofunction. Am J Physiol Heart Circ Physiol. 2022;323(2):H257-H275. doi: 10.1152/ajpheart.00059.2022.
  8. Gozalo AS, Lambert LE, Zerfas PM, Elkins WR. Detection of early myocardial cell death in owl monkeys (Aotus nancymai) using complement component C9 immunohistochemistry in formalin-fixed paraffin-embedded heart tissues: A retrospective study. J Med Primatol. 2022;51(2):93-100. doi: 10.1111/jmp.12567.
  9. Isailă OM, Ion OM, Luta R, Catinas R, Ionita A, et al. Postmortem immunohistochemical findings in early acute myocardial infarction: a systematic review. Int J Mol Sci. 2024;25(14):7625. doi: 10.3390/ijms25147625.
  10. Pakanen L, Appel H, Ahtikoski A, Holm PH, Kreus M, Olsen KB, et al. Primary myocardial fibrosis - a distinct entity characterized by heterogeneous histology. Cardiovasc Pathol. 2023;67:107573. doi: 10.1016/j.carpath.2023.107573.
  11. Junttila MJ, Holmström L, Pylkäs K, Mantere T, Kaikkonen K, Porvari K, et al. Primary myocardial fibrosis as an alternative phenotype pathway of inherited cardiac structural disorders. Circulation. 2018;137:2716-26. doi: 10.1161/circulationaha.117.032175.
  12. Galati G, Leone O, Pasquale F, Olivotto I, Biagini E, Grigioni F, et al. Histological and histometric characterization of myocardial fibrosis in end-stage hypertrophic cardiomyopathy. A clinical-pathological study of 30 explanted hearts. Circ Heart Fail. 2016;9:e003090.
  13. Fu X, Khalil H, Kanisicak O, Boyer JG, Vagnozzi RJ, Maliken BD, et al. Specialized fibroblast differentiated states underlie scar formation in the infarcted mouse heart. J Clin Invest. 2018;128:2127-43. doi: 10.1172/jci98215.
  14. Frantz S, Hundertmark MJ, Schulz-Menger J, Bengel FM, Bauersachs J. Left ventricular remodelling post-myocardial infarction: pathophysiology, imaging, and novel therapies. Eur Heart J. 2022; 43(27):2549-61. doi: 10.1093/eurheartj/ehac223.
  15. Hughes SE. The pathology of hypertrophic cardiomyopathy. Histopathology. 2004;44:412-27. doi: 10.1111/j.1365-2559.2004.01835.x.
  16. Halushka MK, d'Amati G, Bois MC, Fallon JT, et al. Lymphocytic myocarditis: A histopathologic definition and classification from the Society for Cardiovascular Pathology and Association for European Cardiovascular Pathology. I: Endomyocardial biopsy. Cardiovasc Pathol. 2025;78:107759. doi: 10.1016/j.carpath.2025.107759.
  17. Tran K, Milne N, Duhig E, Altman M. Inverted Takotsubo cardiomyopathy – clinicopathologic correlation. Am J Forensic Med Pathol. 2013;34(3):217-21. doi: 10.1097/paf.0b013e31829f653e.
  18. Jiang JP, Downing SE. Catecholamine cardiomyopathy: review and analysis of pathogenetic mechanisms. Yale J Biol Med. 1990;63(6):581-91.
  19. Dewing JM, Saunders V, O'Kelly I. Defining cardiac cell populations and relative cellular composition of the early fetal human heart. PLoS One. 2022;17(11):e0259477. doi: 10.1371/journal.pone. 0259477.
  20. Lennon KM, Saftics A, Abuelreich S, Sahu P, Maddox AL, et al. Cardiac troponin T in extracellular vesicles as a novel biomarker in human cardiovascular disease. Clin Transl Med. 2022;12(8):e979. doi: 10.1002/ctm2.979.
  21. Laurent S, Boutouyrie P. The structural factor of hypertension: large and small artery alterations. Circ Res. 2015;116:1007-21. doi: 10.1161/ circresaha.116.303596.
  22. Fiorino E, Rossin D, Vanni R, Aubry M, Giachino C, Rastaldo R. Recent insights into endogenous mammalian cardiac regeneration post-myocardial infarction. Int J Mol Sci. 2024;25(21):11747. doi: 10.3390/ijms252111747.
  23. Tampakakis E, Kwon C. Heart generation and regeneration. Semin Cell Dev Biol. 2021;118:92-3. doi: 10.1016/j.semcdb.2021.07.014.
  24. Slotvitsky MM, Tsvelaya VA, Podgurskaya AD, Agladze KI. Formation of an electrical coupling between differentiating cardiomyocytes. Sci Rep. 2020;10(1):7774. doi: 10.1038/s41598-020-64581-5.
  25. Iwamiya S, Ihara K, Nitta G, Sasano T. Atrial fibrillation and underlying structural and electrophysiological heterogeneity. Int J Mol Sci. 2024;25(18):10193. doi: 10.3390/ijms251810193.

Published

2026-05-29

How to Cite

Nahirnyi , B., & Vaseruk , A. (2026). Retrospective analysis of the morphofunctional architectonics and pathohistological transformation of the myocardium: from the molecular norm to regenerative potential in remodelling and ischaemia (literature review). Морфологія / Morphologia / Morfologìâ, 20(2), 5–11. https://doi.org/10.26641/1997-9665.2026.2.5-11

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