1. Academic Validation
  2. Role of 8-hydroxyguanine DNA glycosidase 1 deficiency in exacerbating diabetic cardiomyopathy through the regulation of insulin resistance

Role of 8-hydroxyguanine DNA glycosidase 1 deficiency in exacerbating diabetic cardiomyopathy through the regulation of insulin resistance

  • J Mol Cell Cardiol. 2024 Jun 4:194:3-15. doi: 10.1016/j.yjmcc.2024.05.012.
Xiao-Min Li 1 Zi-Jun Wu 2 Jun-Yu Fan 2 Man-Qi Liu 2 Chu-Ge Song 2 Hong-Qiao Chen 2 Yu Yin 2 Ao Li 2 Ya-Hong Wang 2 Sheng-Lan Gao 2 Zhi-Liang Xu 3 Gang Liu 4 Keng Wu 5
Affiliations

Affiliations

  • 1 Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, China; Department of Urology, Changhai Hospital, Navel Medical University (Second Military Medical University), Shanghai 200433, China.
  • 2 Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, China.
  • 3 Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, China. Electronic address: xuzhiliang@gdmu.edu.cn.
  • 4 Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, China; Department of Respiratory and Critical Care Medicine, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China. Electronic address: gangliu11@fmmu.edu.cn.
  • 5 Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, China; Cardiovascular Center, The First Dongguan Affiliated Hospital of Guangdong Medical University, Dongguan 523000, China. Electronic address: wukeng1245@hotmail.com.
Abstract

Diabetic cardiomyopathy (DCM) is a heart failure syndrome, and is one of the major causes of morbidity and mortality in diabetes. DCM is mainly characterized by ventricular dilation, myocardial hypertrophy, myocardial fibrosis and cardiac dysfunction. Clinical studies have found that Insulin resistance is an independent risk factor for DCM. However, its specific mechanism of DCM remains unclear. 8-hydroxyguanine DNA glycosylase 1(OGG1)is involved in DNA base repair and the regulation of inflammatory genes. In this study, we show that OGG1 was associated with the occurrence of DCM. for the first time. The expression of OGG1 was increased in the heart tissue of DCM mice, and OGG1 deficiency aggravated the cardiac dysfunction of DCM mice. Metabolomics show that OGG1 deficiency resulted in obstruction of glycolytic pathway. At the molecular level, OGG1 regulated glucose uptake and Insulin resistance by interacting with PPAR-γ in vitro. In order to explore the protective effect of exogenous OGG1 on DCM, OGG1 adeno-associated virus was injected into DCM mice through tail vein in the middle stage of the disease. We found that the overexpression of OGG1 could improve cardiac dysfunction of DCM mice, indicating that OGG1 had a certain therapeutic effect on DCM. These results demonstrate that OGG1 is a new molecular target for the treatment of DCM and has certain clinical significance.

Keywords

8-hydroxyguanine DNA glycosidase 1; Diabetic cardiomyopathy; Insulin resistance; Peroxisome proliferator activator receptor γ.

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