Molecular Correlates of Early Onset of Diabetic Cardiomyopathy: Possible Therapeutic Targets.

Abstract

Diabetes mellitus (DM) is associated with mitochondrial dysfunction and oxidative stress that can lead to diabetic cardiomyopathy (DCM), which can often remain undetected until late stages of the disease. However, myocardial injury occurs before the onset of measurable cardiac dysfunction, although its molecular correlates are poorly understood. In this study, we made a DM rat induced by a high-fat diet combined with low and high doses of streptozotocin (STZ) to emulate pre and early DCM. RNA-sequencing analysis of ventricular tissue revealed a differential transcriptome profile and abnormal activation of pathways involved in fatty acid metabolism, oxidative phosphorylation, cardiac structure and function, insulin resistance, calcium signalling, apoptosis, and TNF signalling. Moreover, using high glucose-treated human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM), we recapitulated the cardiac cellular phenotype of DM and identified several molecular correlates that may promote the development of DCM. In conclusion, we have developed an experimental framework to target pathways underlying the progression of DCM.

• Authors: Dongjuan Wang, Kun Liu, Jinyan Zhong, Xin Li, Jie Zhang, Gongxin Wang, Ni Li, Tianwen Li, Harvey Davis, Ibrahim El-Gaby, Guoliang Hao, Honghua Ye, Dan Li
• Journal: Oxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2022 Pg. 9014155 ( 2022) ISSN: 1942-0994 [Electronic] United States
• PMID: 35464763 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Dongjuan Wang et al.

Chemical References

• Streptozocin

Topics

• Animals
• Apoptosis
• Diabetes Mellitus, Experimental (drug therapy)
• Diabetic Cardiomyopathies (metabolism)
• Humans
• Induced Pluripotent Stem Cells (metabolism)
• Myocytes, Cardiac (metabolism)
• Oxidative Stress
• Rats
• Streptozocin (adverse effects)