2. Academic Validation
  3. H3 relaxin ameliorates mitochondrial quality control and apoptosis in cardiomyocytes of type 2 diabetic rats via activation of the AMPK pathway

H3 relaxin ameliorates mitochondrial quality control and apoptosis in cardiomyocytes of type 2 diabetic rats via activation of the AMPK pathway

  • Int Immunopharmacol. 2025 Jan 10:144:113664. doi: 10.1016/j.intimp.2024.113664.
Jingzhi Wang 1,  Kelaier Yang 2,  Chunnan Liu 1,  Fan Wang 1,  Xinfang Liang 1,  Jinfeng Wu 3,  Siting Hong 1,  Xinhua Yin 4,  Xiaohui Zhang 5
Affiliations

Affiliations

  • 1 The Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
  • 2 The Department of Endocrinology and Metabolism, Shenzhen University General Hospital, Shenzhen, China.
  • 3 The Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, China.
  • 4 The Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, China; The Department of Cardiology, Shenzhen University General Hospital, Shenzhen, China. Electronic address: [email protected].
  • 5 The Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, China. Electronic address: [email protected].
PMID: 39577222 DOI: 10.1016/j.intimp.2024.113664
Abstract

Purpose: This study aims to explore the protective mechanism of H3 relaxin treatment for type 2 diabetic cardiomyopathy, focusing on its effects on the mitochondrial quality control system and cardiomyocyte Apoptosis.

Methods: A type 2 diabetes rat model was induced with a high-fat diet and streptozotocin. The treatment group received H3 relaxin for 2 weeks. In cellular studies, H9C2 cardiomyocytes were treated with high glucose and palmitic acid, followed by H3 relaxin, MFN2 lentivirus, and AMPK Inhibitor compound C. Mitochondrial quality control, membrane potential, ROS, and Apoptosis markers were assessed.

Results: H3 relaxin improved Apoptosis markers, reduced mitochondrial fission (Drp1, Fis1) and Mitophagy proteins (parkin, PINK1), and increased mitochondrial fusion proteins (MFN2, OPA1). It restored mitochondrial membrane potential, lowered ROS, and showed anti-apoptotic effects dependent on MFN2. AMPK pathway activation by H3 relaxin was crucial, as compound C largely negated these benefits.

Conclusion: H3 relaxin improves the mitochondrial quality control system and reduces high glucose and palmitic acid-induced Apoptosis by upregulating MFN2. This protective effect is achieved through the activation of the AMPK pathway.

Keywords

AMPK signalling pathway; Cell apoptosis; Diabetic cardiomyopathy; H3 relaxin; Mitochondrial quality control.

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