Heller Katja, Flocke Vera, Straub Tamara, Ding Zhaoping, Srivastava Tanu, Nowak Melissa, Funk Florian, Levkau Bodo, Schmitt Joachim, Grandoch Maria, Flögel Ulrich
Institute for Translational Pharmacology, Medical Faculty, University Clinics and Heinrich Heine University, Düsseldorf, Germany.
Experimental Cardiovascular Imaging, Institute for Molecular Cardiology, Heinrich Heine University, Düsseldorf, Germany.
Npj Imaging. 2024 Sep 23;2(1):36. doi: 10.1038/s44303-024-00044-0.
People with diabetes have an increased cardiovascular risk and a poorer outcome after myocardial infarction (MI). However, the exact underlying mechanisms are still unclear, as is the question of which non-invasive measures could be used to predict the altered risk for the patient at early stages of the disease and adapt personalized treatment. Here, we used a holistic magnetic resonance approach to monitor longitudinally not only the main target heart, but also liver, peripheral/skeletal muscle, bone marrow, and hematopoiesis during disease development and subsequent MI. In prediabetic mice, we found a strong accumulation of lipids in all organs which preceded even a significant whole-body weight gain. Intramyocellular lipids (IMCLs) were most sensitive to reveal in vivo very early alterations in tissue properties during the prediabetic state. Subsequent induction of MI led to a persistent impairment of contractile function in septal/posterior segments of prediabetic hearts which correlated with their lipid load prior MI. At the same time, prediabetic cardiomyocytes exhibited sarcomere function at its limit resulting in overload and lower compensatory contractility of the healthy myocardium after MI. In summary, we identified IMCLs as very early marker in murine prediabetes and together with the cardiac lipid load as predictive for the functional outcome after MI.
糖尿病患者心血管风险增加，心肌梗死（MI）后预后较差。然而，确切的潜在机制仍不清楚，同样不清楚的是哪些非侵入性措施可用于在疾病早期预测患者风险变化并调整个性化治疗。在此，我们采用整体磁共振方法，在疾病发展及随后的心肌梗死过程中，纵向监测不仅主要靶器官心脏，还包括肝脏、外周/骨骼肌、骨髓和造血情况。在糖尿病前期小鼠中，我们发现所有器官中脂质大量蓄积，甚至早于显著的全身体重增加。肌细胞内脂质（IMCLs）对揭示糖尿病前期状态下体内组织特性的极早期变化最为敏感。随后诱发的心肌梗死导致糖尿病前期心脏的间隔/后段收缩功能持续受损，这与其心肌梗死前的脂质负荷相关。与此同时，糖尿病前期心肌细胞的肌节功能处于极限，导致心肌梗死后健康心肌负荷过重且代偿性收缩力降低。总之，我们确定IMCLs为小鼠糖尿病前期的极早期标志物，并与心脏脂质负荷一起可预测心肌梗死后的功能结局。
