Global ischemia induces stemness and dedifferentiation in human adult cardiomyocytes after cardiac arrest

• Published in: Scientific reports Vol. 14; no. 1; pp. 14256 - 10
• Main Authors: Jinton, Helen, Sopasakis, Victoria Rotter, Sjölin, Linnéa, Oldfors, Anders, Jeppsson, Anders, Oras, Jonatan, Wernbom, Mathias, Vukusic, Kristina
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 20.06.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/532; 631/80; 692/308; 692/4019; Adult; Aged; Animal models; Atrioventricular junction; Biomarkers; Biomarkers - metabolism; Biopsy; Cardiac and Cardiovascular Systems; Cardiac arrest; Cardiomyocyte proliferation; Cardiomyocytes; Cell Dedifferentiation; Cell proliferation; Cerebral blood flow; Dedifferentiation; Female; Heart; Heart Arrest - metabolism; Heart Arrest - pathology; Heart Ventricles - metabolism; Heart Ventricles - pathology; Humanities and Social Sciences; Humans; Hypoxia; Immunohistochemistry; Ischemia; Kardiologi; Male; MDR1 protein; Middle Aged; multidisciplinary; Myocytes; Myocytes, Cardiac - cytology; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - pathology; Nkx2.5 protein; Organ donors; Proliferating cell nuclear antigen; Regeneration; Science; Science (multidisciplinary); Stem cell transplantation; Stem cells; Stem Cells - cytology; Stem Cells - metabolism; Troponin; Troponin T; Troponin T - metabolism; Ventricle; Heart; Cardiomyocyte proliferation; Regeneration; Dedifferentiation; Cardiac arrest; Atrioventricular junction; Stem cells; Hypoxia
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-65212-z

Global ischemia has been shown to induce cardiac regenerative response in animal models. One of the suggested mechanisms behind cardiac regeneration is dedifferentiation of cardiomyocytes. How human adult cardiomyocytes respond to global ischemia is not fully known. In this study, biopsies from the left ventricle (LV) and the atrioventricular junction (AVj), a potential stem cell niche, were collected from multi-organ donors with cardiac arrest (N = 15) or without cardiac arrest (N = 6). Using immunohistochemistry, we investigated the expression of biomarkers associated with stem cells during cardiomyogenesis; MDR1, SSEA4, NKX2.5, and WT1, proliferation markers PCNA and Ki67, and hypoxia responsive factor HIF1α. The myocyte nuclei marker PCM1 and cardiac Troponin T were also included. We found expression of cardiac stem cell markers in a subpopulation of LV cardiomyocytes in the cardiac arrest group. The same cells showed a low expression of Troponin T indicating remodeling of cardiomyocytes. No such expression was found in cardiomyocytes from the control group. Stem cell biomarker expression in AVj was more pronounced in the cardiac arrest group. Furthermore, co-expression of PCNA and Ki67 with PCM1 was only found in the cardiac arrest group in the AVj. Our results indicate that a subpopulation of human cardiomyocytes in the LV undergo partial dedifferentiation upon global ischemia and may be involved in the cardiac regenerative response together with immature cardiomyocytes in the AVj.