Cyclic stretch promotes vascular homing of endothelial progenitor cells via Acsl1 regulation of mitochondrial fatty acid oxidation.
Yue HanJing YanZhi-Yin LiYang-Jing FanZong-Lai JiangJohn Y-J ShyyShu ChienPublished in: Proceedings of the National Academy of Sciences of the United States of America (2023)
Endothelial progenitor cells (EPCs) play an important role in vascular repair and re-endothelialization after vessel injury. EPCs in blood vessels are subjected to cyclic stretch (CS) due to the pulsatile pressure, but the role of CS in metabolic reprogramming of EPC, particularly its vascular homing and repair, is largely unknown. In the current study, physiological CS applied to EPCs at a magnitude of 10% and a frequency of 1 Hz significantly promoted their vascular adhesion and endothelial differentiation. CS enhanced mitochondrial elongation and oxidative phosphorylation (OXPHOS), as well as adenosine triphosphate production. Metabolomic study and Ultra-high performance liquid chromatography-mass spectrometry assay revealed that CS significantly decreased the content of long-chain fatty acids (LCFAs) and markedly induced long-chain fatty acyl-CoA synthetase 1 (Acsl1), which in turn facilitated the catabolism of LCFAs in mitochondria via fatty acid β-oxidation and OXPHOS. In a rat carotid artery injury model, transplantation of EPCs overexpressing Acsl1 enhanced the adhesion and re-endothelialization of EPCs in vivo. MRI and vascular morphology staining showed that Acsl1 overexpression in EPCs improved vascular repair and inhibited vascular stenosis. This study reveals a mechanotransduction mechanism by which physiological CS enhances endothelial repair via EPC patency.
Keyphrases
- fatty acid
- mass spectrometry
- endothelial cells
- oxidative stress
- magnetic resonance imaging
- mesenchymal stem cells
- tandem mass spectrometry
- ultra high performance liquid chromatography
- magnetic resonance
- hydrogen peroxide
- cell death
- high throughput
- transcription factor
- simultaneous determination
- high resolution mass spectrometry
- escherichia coli
- living cells
- quantum dots
- cell migration
- gas chromatography
- solid phase extraction
- flow cytometry