Hernandez Ivana, Chithiravelu Gobinath, Padilla Andie E, Joddar Binata
Inspired Materials and Stem-Cell Based Tissue Engineering Laboratory (IMSTEL), School of Chemical, Biological, and Environmental Engineering, Oregon State University, Corvallis, OR 97330 USA.
Biomedical Engineering Program, Department of Metallurgical, Materials, and Biomedical Engineering, M201 Engineering, The University of Texas at El Paso, 500 W. University Avenue, El Paso, TX 79968 USA.
Discov Appl Sci. 2025;7(7):788. doi: 10.1007/s42452-025-07442-y. Epub 2025 Jul 15.
This study aimed to elucidate the impact of advanced glycation end products (AGEs) and glucose shock on cardiomyocyte viability, gene expression, cardiac biomarkers, and cardiac contractility. Firstly, AGEs were generated in-house, and their concentration was confirmed using absorbance measurements. AC16 cardiomyocytes were then exposed to varying doses of AGEs, resulting in dose-dependent decreases in cell viability. The maximum tolerated dose of AGEs was determined, revealing significant downregulation of the cardiac gene gap junction alpha 1 (GJA1). Furthermore, the study assessed the effects of AGEs, glucose shock, and their combination on biomarkers, cardiac myosin heavy chain (MHC) and connexin-43 (Cx-43), in AC16 cells. It was found that AGEs supplementation induced an increase in MHC expression while reducing Cx-43 expression, potentially contributing to cardiac dysfunction. Glucose shock also affected cardiomyocyte contractility, highlighting the complex interplay between AGEs, glucose levels, and cardiac function. Additionally, human iPSC-derived cardiomyocytes were subjected to varying doses of AGEs, revealing dose-dependent cytotoxicity and alterations in contractility. Immunostaining confirmed upregulation of MYH7, a cardiac gene associated with muscle contraction, in response to AGEs. However, the expression of Cx-43 was minimal in these cells. This investigation sheds light on the intricate relationship between AGEs, glucose shock, and cardiomyocyte function, providing insights into potential mechanisms underlying cardiac dysfunction associated with metabolic disorders such as diabetic cardiomyopathy (DCM).
The online version contains supplementary material available at 10.1007/s42452-025-07442-y.
本研究旨在阐明晚期糖基化终产物（AGEs）和葡萄糖冲击对心肌细胞活力、基因表达、心脏生物标志物及心脏收缩性的影响。首先，在内部生成AGEs，并通过吸光度测量确认其浓度。然后将AC16心肌细胞暴露于不同剂量的AGEs中，导致细胞活力呈剂量依赖性下降。确定了AGEs的最大耐受剂量，发现心脏基因缝隙连接蛋白α1（GJA1）显著下调。此外，该研究评估了AGEs、葡萄糖冲击及其组合对AC16细胞中生物标志物、心肌肌球蛋白重链（MHC）和连接蛋白43（Cx-43）的影响。发现补充AGEs会导致MHC表达增加，同时降低Cx-43表达，这可能导致心脏功能障碍。葡萄糖冲击也影响心肌细胞收缩性，突出了AGEs、葡萄糖水平和心脏功能之间复杂的相互作用。此外，对人诱导多能干细胞衍生的心肌细胞施加不同剂量的AGEs，发现具有剂量依赖性细胞毒性和收缩性改变。免疫染色证实，响应AGEs，与肌肉收缩相关的心脏基因MYH7上调。然而，这些细胞中Cx-43的表达极少。本研究揭示了AGEs、葡萄糖冲击与心肌细胞功能之间的复杂关系，为糖尿病性心肌病（DCM）等代谢紊乱相关心脏功能障碍的潜在机制提供了见解。
在线版本包含可在10.1007/s42452-025-07442-y获取的补充材料。
