2. Academic Validation
  3. Targeting long-chain acylcarnitine accumulation to protect cardiac mitochondrial homeostasis after complete revascularization

Targeting long-chain acylcarnitine accumulation to protect cardiac mitochondrial homeostasis after complete revascularization

  • Cell Rep Med. 2025 Dec 16;6(12):102507. doi: 10.1016/j.xcrm.2025.102507.
Rui Lin 1,  Yuyu Li 1,  Shiwei Yang 1,  Hai Gao 1,  Fengjuan Li 1,  Xue Wang 1,  Xin Tan 1,  Zhengkai Wang 1,  Weiyao Chen 1,  Lu Ren 1,  Xiujie Wang 2,  Li Wang 3,  Jun Qin 4,  Wenjie Yin 5,  Jie Du 6,  Yuan Wang 7
Affiliations

Affiliations

  • 1 Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Diseases, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing 100029, China.
  • 2 Key Laboratory of Genetic Networks, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
  • 3 State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Beijing 100037, China.
  • 4 State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (The PHOENIX Center, Beijing), Beijing 102206, China.
  • 5 Department of Hypertension, The First Hospital of Shanxi Medical University, Shanxi 030000, China.
  • 6 Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Diseases, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing 100029, China. Electronic address: [email protected].
  • 7 Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Diseases, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing 100029, China. Electronic address: [email protected].
PMID: 41406945 DOI: 10.1016/j.xcrm.2025.102507
Abstract

Approximately 20% of acute myocardial infarction (AMI) patients with multivessel disease experience adverse outcomes after complete revascularization. We aim to investigate the underlying metabolic mechanism of ischemia-reperfusion injury responsible for abnormal hemodynamic stresses in high-risk patients undergoing complete revascularization. Elevated preoperative serum levels of long-chain acylcarnitine (LCAC) 16:1 are associated with an increased risk of poor prognosis following complete revascularization. Multi-omics analyses reveal that reperfusion injury activates fatty acid degradation, and carnitine palmitoyltransferase 1A (CPT1A) is identified as a key regulator of LCACs in the interaction network in porcine models. In the early stages of reperfusion injury in non-culprit lesions, the release and prolonged elevation of circulating LCACs primarily depend on the activation of endothelial CPT1A through hemodynamic injury, which can be reduced using an inhibitor (etomoxir). Excess LCACs enter cardiomyocytes via the organic cation transporter 2, leading to imbalanced mitochondrial quality control and causing cardiomyocyte death.

Keywords

CPT1A; complete revascularization; hemodynamic shear stress; long-chain acylcarnitine metabolism; non-culprit lesion; reperfusion injury.

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