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  3. Modeling diabetic cardiomyopathy using human cardiac organoids: Effects of high glucose and lipid conditions

Modeling diabetic cardiomyopathy using human cardiac organoids: Effects of high glucose and lipid conditions

  • Chem Biol Interact. 2025 Apr 25:411:111421. doi: 10.1016/j.cbi.2025.111421.
Xiangyu Wang 1,  Xin Tan 1,  Ting Zhang 2,  Shuai Xu 1,  Yiyao Zeng 1,  Anchen Xu 1,  Xian Li 1,  Ge Zhang 3,  Yufeng Jiang 1,  Hezi Jiang 1,  Jili Fan 4,  Xiaohong Bo 4,  Huimin Fan 5,  Yafeng Zhou 6
Affiliations

Affiliations

  • 1 Department of Cardiology, The Fourth Affiliated Hospital of Soochow University, Suzhou Dushu Lake Hospital, Medical Center of Soochow University, Suzhou, 215000, China; Institute for Hypertension, Soochow University, Suzhou, 215000, China.
  • 2 Department of Cardiology, The Fourth Affiliated Hospital of Soochow University, Suzhou Dushu Lake Hospital, Medical Center of Soochow University, Suzhou, 215000, China; Institute for Hypertension, Soochow University, Suzhou, 215000, China; Department of Cardiology, The Second People's Hospital of Hefei, Hefei Hospital Affiliated to Ahhui Medical University, Hefei, 230011, China.
  • 3 Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
  • 4 Department of Cardiovascular Disease, Taihe County People's Hospital, Fuyang, 236600, China.
  • 5 Department of Cardiology, The Fourth Affiliated Hospital of Soochow University, Suzhou Dushu Lake Hospital, Medical Center of Soochow University, Suzhou, 215000, China; Center of Translational Medicine and Clinical Laboratory, The Fourth Affiliated Hospital to Soochow University, Suzhou Dushu Lake Hospital, Suzhou, 215028, China. Electronic address: fhm_sunshine@163.com.
  • 6 Department of Cardiology, The Fourth Affiliated Hospital of Soochow University, Suzhou Dushu Lake Hospital, Medical Center of Soochow University, Suzhou, 215000, China; Institute for Hypertension, Soochow University, Suzhou, 215000, China. Electronic address: Dryafengzhou@163.com.
PMID: 39984109 DOI: 10.1016/j.cbi.2025.111421
Abstract

Diabetic cardiomyopathy (DCM) is a complex metabolic disorder resulting from chronic hyperglycemia and lipid toxicity, which leads to cardiac dysfunction, fibrosis, inflammation, and mitochondrial impairment. Traditional two-dimensional (2D) cell cultures and animal models have limitations in replicating human cardiac physiology and pathophysiology. In this study, we successfully developed a three-dimensional (3D) model of DCM using cardiac organoids generated from human induced pluripotent stem cells (hiPSCs). These organoids were treated with varying concentrations of glucose and sodium palmitate to mimic the high-glucose and high-lipid environment associated with diabetes. At lower concentrations, glucose and sodium palmitate enhanced cell viability, while higher concentrations induced significant cardiotoxic effects, including Apoptosis, oxidative stress, and mitochondrial dysfunction. The cardiac organoids also exhibited increased expression of cardiac injury markers, fibrosis-related genes, and inflammatory cytokines under high-glucose and high-lipid conditions. Treatment with metformin, a widely used antidiabetic drug, mitigated these adverse effects, indicating the model's potential for drug testing and evaluation. Our findings demonstrate that this human-derived 3D cardiac Organoid model provides a more physiologically relevant platform for studying DCM and can effectively complement traditional models. This model holds promise for advancing the understanding of diabetic heart disease and for assessing the efficacy of potential therapeutic interventions.

Keywords

Cardiac organoids; Diabetic cardiomyopathy; Hyperglycemia; Lipotoxicity; Metformin.

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