1. Academic Validation
  2. Roles of heat shock protein A12A in the development of diabetic cardiomyopathy

Roles of heat shock protein A12A in the development of diabetic cardiomyopathy

  • Cell Stress Chaperones. 2024 Mar 12;29(2):272-284. doi: 10.1016/j.cstres.2024.03.004.
Yunxiao Jia 1 Yunhao Yu 1 Chenxi Gao 1 Yuehua Li 2 Chuanfu Li 3 Zhengnian Ding 4 Qiuyue Kong 5 Li Liu 6
Affiliations

Affiliations

  • 1 Department of Geriatrics, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
  • 2 Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing, Jiangsu Province, China.
  • 3 Departments of Surgery, East Tennessee State University, Johnson City, TN, USA.
  • 4 Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
  • 5 Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China. Electronic address: kongqiuyue@njmu.edu.cn.
  • 6 Department of Geriatrics, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China; Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing, Jiangsu Province, China. Electronic address: liuli@njmu.edu.cn.
Abstract

Long-term hyperglycemia can lead to diabetic cardiomyopathy (DCM), a main lethal complication of diabetes. However, the mechanisms underlying DCM development have not been fully elucidated. Heat shock protein A12A (HSPA12A) is the atypic member of the Heat shock 70kDa protein family. In the present study, we found that the expression of HSPA12A was upregulated in the hearts of mice with streptozotocin-induced diabetes, while ablation of HSPA12A improved cardiac systolic and diastolic dysfunction and increased cumulative survival of diabetic mice. An increased expression of HSPA12A was also found in H9c2 cardiac cells following treatment with high glucose (HG), while overexpression of HSPA12A-enhanced the HG-induced cardiac cell death, as reflected by higher levels of propidium iodide cells, Lactate Dehydrogenase leakage, and Caspase 3 cleavage. Moreover, the HG-induced increase of oxidative stress, as indicated by dihydroethidium staining, was exaggerated by HSPA12A overexpression. Further studies demonstrated that the HG-induced increases of protein kinase B and forkhead box transcription factors 1 phosphorylation were diminished by HSPA12A overexpression, while pharmacologically inhibition of protein kinase B further enhanced the HG-induced Lactate Dehydrogenase leakage in HSPA12A overexpressed cardiac cells. Together, the results suggest that hyperglycemia upregulated HSPA12A expression in cardiac cells, by which induced cell death to promote DCM development. Targeting HSPA12A may serve as a potential approach for DCM management.

Keywords

AKT/FOXO1 signaling; Cardiac cell injury; Diabetic cardiomyopathy (DCM); Heat shock protein A12A (HSPA12A); High glucose.

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