Cyclic stretch promotes vascular homing of endothelial progenitor cells via Acsl1 regulation of mitochondrial fatty acid oxidation

Author:

Han Yue1ORCID,Yan Jing1,Li Zhi-Yin1,Fan Yang-Jing1,Jiang Zong-Lai1ORCID,Shyy John Y.-J.23ORCID,Chien Shu234ORCID

Affiliation:

1. Institute of Mechanobiology and Medical Engineering, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Minhang, Shanghai 200240, China

2. Department of Medicine, University of California, San Diego, La Jolla, CA 92093

3. Institute of Engineering in Medicine, University of California, San Diego, La Jolla, CA 92093

4. Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093

Abstract

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.

Funder

National Natural Science Foundation of China

National Institute of Health NHLBI

National Institute's of Health NHLBI

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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