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
Department of Molecular Genetics, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands.
Department of Vascular Surgery, Erasmus MC Cardiovascular Institute, Erasmus University Medical Center, Room 702A, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands.
Mol Imaging Biol. 2024 Aug;26(4):628-637. doi: 10.1007/s11307-024-01902-4. Epub 2024 Mar 18.
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.
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.
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.
在本研究中，我们利用功能性微型计算机断层扫描（micro-CT）和荧光分子断层扫描（FMT）成像技术，在Ercc1突变小鼠中探索细胞凋亡作为心力衰竭潜在生物标志物的作用。Ercc1参与多种DNA修复途径，其突变会导致人类和小鼠加速衰老表型，这是由于损害重要DNA功能的DNA损伤积累所致。我们先前发现，小鼠中Ercc1的全身突变和心肌细胞特异性缺失会导致老年时左心室（LV）功能障碍。
在此我们报告，功能性micro-CT和FMT成像相结合使我们能够在明显的LV功能障碍出现之前检测系统性Ercc1突变小鼠中的细胞凋亡，这表明其作为心脏损伤的早期指标和促成因素的潜力。早在12周龄时，即使整体LV功能看起来正常，体内检测细胞凋亡也是可行的，这突出了细胞凋亡作为LV功能障碍早期预测指标的潜力，LV功能障碍随后在24周时出现。
本研究强调了功能性micro-CT和FMT成像相结合在评估心脏功能和检测细胞凋亡方面的实用性，为细胞凋亡作为心力衰竭早期生物标志物的潜力提供了有价值的见解。
