L‐carnitine alleviates cardiac microvascular dysfunction in diabetic cardiomyopathy by enhancing PINK1‐Parkin‐dependent mitophagy through the CPT1a‐PHB2‐PARL pathways

• DOI: 10.1111/apha.13975
• Publication Date: 2023-04-12T11:07:43Z
• Authors: Su Li; Muyin Liu; Jinxiang Chen; Yuqiong Chen; Ming Yin; You Zhou; Qiyu Li; Fei Xu; Youran Li; Xiaopei Yan; Yan Xia; Ao Chen; Danbo Lu; Chenguang Li; Li Shen; Zhangwei Chen; Juying Qian; Junbo Ge
• Keywords: PINK1; MFN2; Optineurin

Abstract Aim To explore the beneficial effects of L‐carnitine on cardiac microvascular dysfunction in diabetic cardiomyopathy from perspectives mitophagy and mitochondrial integrity. Methods Male db/db db/m mice were randomly assigned to groups treated with or a solvent for 24 weeks. Endothelium‐specific PARL overexpression was attained via adeno‐associated virus serotype 9 (AAV9) transfection. Adenovirus (ADV) vectors overexpressing wild‐type CPT1a, mutant transfected into endothelial cells exposed high glucose free fatty acid (HG/FFA) injury. Cardiac function, mitophagy, function analyzed by immunofluorescence transmission electron microscopy. Protein expression interactions assessed western blotting immunoprecipitation. Results treatment enhanced perfusion, reinforced barrier repressed inflammatory response, maintained structure mice. Further results demonstrated that PINK1‐Parkin‐dependent suppressed suffering injury, these largely alleviated through inhibition detachment PHB2. Moreover, CPT1a modulated PHB2‐PARL interaction directly binding The increase activity induced amino mutation (M593S) interaction, thereby improving function. In contrast, inhibited abolished all integrity Conclusion maintaining reversing injury cardiomyopathy.