Hybrid Molecular and Functional Micro-CT Imaging Reveals Increased Myocardial Apoptosis Preceding Cardiac Failure in Progeroid Ercc1 Mice

• Published in: Molecular imaging and biology Vol. 26; no. 4; pp. 628 - 637
• Main Authors: van Thiel, Bibi S., de Boer, Martine, Ridwan, Yanto, de Kleijnen, Marion G. J., van Vliet, Nicole, van der Linden, Janette, de Beer, Isa, van Heijningen, Paula M., Vermeij, Wilbert P., Hoeijmakers, Jan H. J., Danser, A. H. Jan, Kanaar, Roland, Duncker, Dirk J., van der Pluijm, Ingrid, Essers, Jeroen
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.08.2024; Springer Nature B.V
• Subjects: Aging; Animals; Apoptosis; Biomarkers; Cardiomyocytes; Computed tomography; Deoxyribonucleic acid; DNA; DNA repair; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Endonucleases - genetics; Endonucleases - metabolism; ERCC1 protein; Failure; Functionals; Gene deletion; Heart Failure - diagnostic imaging; Heart Failure - pathology; Imaging; Imaging techniques; In vivo methods and tests; Medical imaging; Medicine; Medicine & Public Health; Mice; Mutants; Mutation; Myocardium - pathology; Phenotypes; Radiology; Research Article; X-Ray Microtomography; Molecular imaging; Heart failure; CT; Ercc1; Aging; FMT; DNA repair
• ISSN: 1536-1632; 1860-2002; 1860-2002
• DOI: 10.1007/s11307-024-01902-4

Purpose In this study, we explored the role of apoptosis as a potential biomarker for cardiac failure using functional micro-CT and fluorescence molecular tomography (FMT) imaging techniques in Ercc1 mutant mice. Ercc1 is involved in multiple DNA repair pathways, and its mutations contribute to accelerated aging phenotypes in both humans and mice, due to the accumulation of DNA lesions that impair vital DNA functions. We previously found that systemic mutations and cardiomyocyte-restricted deletion of Ercc1 in mice results in left ventricular (LV) dysfunction at older age. Procedures and Results Here we report that combined functional micro-CT and FMT imaging allowed us to detect apoptosis in systemic Ercc1 mutant mice prior to the development of overt LV dysfunction, suggesting its potential as an early indicator and contributing factor of cardiac impairment. The detection of apoptosis in vivo was feasible as early as 12 weeks of age, even when global LV function appeared normal, underscoring the potential of apoptosis as an early predictor of LV dysfunction, which subsequently manifested at 24 weeks. Conclusions This study highlights the utility of combined functional micro-CT and FMT imaging in assessing cardiac function and detecting apoptosis, providing valuable insights into the potential of apoptosis as an early biomarker for cardiac failure.