Developmental Angiogenesis Requires the Mitochondrial Phenylalanyl-tRNA Synthetase

Bowen Li; Bowen Li; Kun Chen; Fangfang Liu; Juan Zhang; Xihui Chen; Xihui Chen; Tangdong Chen; Tangdong Chen; Qi Chen; Qi Chen; Yan Yao; Weihong Hu; Li Wang; Li Wang; Li Wang; Yuanming Wu; Yuanming Wu

doi:10.3389/fcvm.2021.724846

Frontiers in Cardiovascular Medicine (Sep 2021)

Developmental Angiogenesis Requires the Mitochondrial Phenylalanyl-tRNA Synthetase

Bowen Li,
Bowen Li,
Kun Chen,
Fangfang Liu,
Juan Zhang,
Xihui Chen,
Xihui Chen,
Tangdong Chen,
Tangdong Chen,
Qi Chen,
Qi Chen,
Yan Yao,
Weihong Hu,
Li Wang,
Li Wang,
Li Wang,
Yuanming Wu,
Yuanming Wu

Affiliations

Bowen Li: Department of Biochemistry and Molecular Biology, Air Force Medical University, Xi'an, China
Bowen Li: Shaanxi Provincial Key Laboratory of Clinic Genetics, Air Force Medical University, Xi'an, China
Kun Chen: Department of Anatomy, Histology and Embryology and K.K. Leung Brain Research Centre, Air Force Medical University, Xi'an, China
Fangfang Liu: Department of Neurosciences, Air Force Medical University, Xi'an, China
Juan Zhang: Department of Biochemistry and Molecular Biology, College of Life Sciences, Northwest University, Xi'an, China
Xihui Chen: Department of Biochemistry and Molecular Biology, Air Force Medical University, Xi'an, China
Xihui Chen: Shaanxi Provincial Key Laboratory of Clinic Genetics, Air Force Medical University, Xi'an, China
Tangdong Chen: Department of Biochemistry and Molecular Biology, Air Force Medical University, Xi'an, China
Tangdong Chen: Shaanxi Provincial Key Laboratory of Clinic Genetics, Air Force Medical University, Xi'an, China
Qi Chen: Department of Biochemistry and Molecular Biology, Air Force Medical University, Xi'an, China
Qi Chen: Shaanxi Provincial Key Laboratory of Clinic Genetics, Air Force Medical University, Xi'an, China
Yan Yao: Department of Clinical Medicine, Yan'an University, Yan'an, China
Weihong Hu: Department of Clinical Medicine, Yan'an University, Yan'an, China
Li Wang: Department of Biochemistry and Molecular Biology, Air Force Medical University, Xi'an, China
Li Wang: Shaanxi Provincial Key Laboratory of Clinic Genetics, Air Force Medical University, Xi'an, China
Li Wang: School of Aerospace Medicine, Air Force Medical University, Xi'an, China
Yuanming Wu: Department of Biochemistry and Molecular Biology, Air Force Medical University, Xi'an, China
Yuanming Wu: Shaanxi Provincial Key Laboratory of Clinic Genetics, Air Force Medical University, Xi'an, China

DOI: https://doi.org/10.3389/fcvm.2021.724846
Journal volume & issue: Vol. 8

Abstract

Read online

Background: Mitochondrial aminoacyl-tRNA synthetases (mtARSs) catalyze the binding of specific amino acids to their cognate tRNAs and play an essential role in the synthesis of proteins encoded by mitochondrial DNA. Defects in mtARSs have been linked to human diseases, but their tissue-specific pathophysiology remains elusive. Here we examined the role of mitochondrial phenylalanyl-tRNA synthetase (FARS2) in developmental angiogenesis and its potential contribution to the pathogenesis of cardiovascular disease.Methods: Morpholinos were injected into fertilized zebrafish ova to establish an in vivo fars2 knock-down model. A visualization of the vasculature was achieved by using Tg (fli1: EGFP)y1 transgenic zebrafish. In addition, small interference RNAs (siRNAs) were transferred into human umbilical vein endothelial cells (HUVECs) to establish an in vitro FARS2 knock-down model. Cell motility, proliferation, and tubulogenesis were determined using scratch-wound CCK8, transwell-based migration, and tube formation assays. In addition, mitochondria- and non-mitochondria-related respiration were evaluated using a Seahorse XF24 analyzer and flow cytometry assays. Analyses of the expression levels of transcripts and proteins were performed using qRT-PCR and western blotting, respectively.Results: The knock-down of fars2 hampered the embryonic development in zebrafish and delayed the formation of the vasculature in Tg (fli1: EGFP)y1 transgenic zebrafish. In addition, the siRNA-mediated knock-down of FARS2 impaired angiogenesis in HUVECs as indicated by decreased cell motility and tube formation capacity. The knock-down of FARS2 also produced variable decreases in mitochondrial- and non-mitochondrial respiration in HUVECs and disrupted the regulatory pathways of angiogenesis in both HUVECs and zebrafish.Conclusion: Our current work offers novel insights into angiogenesis defects and cardiovascular diseases induced by FARS2 deficiency.

Published in Frontiers in Cardiovascular Medicine

ISSN: 2297-055X (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the circulatory (Cardiovascular) system
Website: https://www.frontiersin.org/journals/cardiovascular-medicine

About the journal

Abstract

Keywords