Blueprint of the distinct metabolite profiles of healthy pig heart chambers

Authors: HAIKONEN, RETU - University Of Eastern Finland; MEURONEN, TOPI - University Of Turku; KOISTINEN, VILLE - University Of Eastern Finland; KARKKAINEN, OLLI - University Of Eastern Finland; TUOMAINEN, TOMI - University Of Eastern Finland; Solano Aguilar, Gloria; URBAN JR., JOSEPH - Former ARS Employee; LEHTONEN, MARKO - University Of Eastern Finland; TAVI, PASI - University Of Eastern Finland; HANHINEVA, KATI - University Of Eastern Finland

Submitted to: Journal of Molecular and Cellular Cardiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/8/2025
Publication Date: 6/10/2025
Citation: Haikonen, R., Meuronen, T., Koistinen, V., Karkkainen, O., Tuomainen, T., Solano Aguilar, G., Urban Jr., J.F., Lehtonen, M., Tavi, P., Hanhineva, K. 2025. Blueprint of the distinct metabolite profiles of healthy pig heart chambers. Journal of Molecular and Cellular Cardiology. 13. Article 100462. https://doi.org/10.1016/j.jmccpl.2025.100462.
DOI: https://doi.org/10.1016/j.jmccpl.2025.100462

Interpretive Summary: The most prevalent heart diseases are chamber-specific, although they are often studied as diseases affecting the whole heart and from distal samples like serum or plasma. This study aims to comprehensively characterize the chamber-specific metabolic profiles of all four heart chambers in a healthy animal model close to human metabolism, pigs. We employed liquid chromatography-mass spectrometry metabolomics to analyze the metabolite profiles of all four heart chambers in thirty healthy pigs maintained on an ad-libitum diet and housed under standard, non-stressed physiological conditions. Our findings reveal differences in electron transport chain-related metabolites such as NAD+ and FAD. Additionally, hexose-phosphates and several acylcarnitines exhibited chamber-dependent variations in abundance. The ventricles, particularly the left, demonstrated distinct redox states, with differential levels of glutathione and ascorbic acid, suggesting variations in oxidative stress across chambers. Furthermore, amino acids had chambers-specific abundance patterns and ventricles showed an increased requirement for protein synthesis, likely associated with repair mechanisms following reactive oxygen species (ROS)-induced cellular damage. These findings provide a distinct metabolite profile for each heart chamber, establishing a foundation for future metabolomics studies aimed at advancing the understanding of chamber-specific alterations in the metabolic processes in health and disease.

Technical Abstract: The heart is one of the most studied organs, with physiological processes and disease research. While it is well-established that significant structural and functional differences exist between the chambers, most studies focus on only a single heart chamber, predominantly the left ventricle. This study aims to comprehensively characterise the chamber-specific metabolic profiles of all four heart chambers in a healthy animal model close to human metabolism, pigs. We employed liquid chromatography-mass spectrometry metabolomics to analyse the metabolite profiles of heart chambers in healthy pigs (N = 30) maintained on an ad libitum diet and housed under standard, non-stressed physiological conditions. Our findings reveal a higher energy demand in the left ventricle, as evidenced by elevated levels of electron transport chain-related metabolites such as NAD+ and FAD. Additionally, hexose-phosphates and several acylcarnitines exhibited chamber-dependent variations in abundance. The ventricles, particularly the left, demonstrated distinct redox states, with differential levels of glutathione and ascorbic acid, suggesting variations in oxidative stress across chambers. Furthermore, amino acids had chamber-specific abundance patterns, and ventricles showed an increased requirement for protein synthesis, likely associated with repair mechanisms following reactive oxygen species (ROS)-induced cellular damage. Our study reveals significant differences in the metabolic profiles across four heart chambers in healthy pig hearts, underscoring the metabolic heterogeneity of cardiac tissue. These findings highlight the necessity of investigating chamber-specific metabolic pathways to better understand heart functionality. Such insights could inform the development of more precise therapeutic strategies tailored to metabolic demands and functional roles in heart chambers.