Jiahe Wu, Yi Lu, Xinchen Gao, Xiaorong Hu, Zhibing Lu, Chenze Li
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引用次数: 0
Abstract
Aims: Protein glycosylation regulated by glycosyltransferases is an important type of post-translational modification. The role of the glycosyltransferase genes (GTGs) in heart failure (HF) remains unclear and requires further investigation.
Methods: Differential expression analysis was performed on the transverse aortic constriction (TAC)-related dataset GSE36074 to screen out the differentially expressed GTGs. Enrichment and protein-protein interaction analyses explored their functional mechanisms and interconnections. Pearson correlation analysis revealed the relationship between GTGs and pathological cardiac remodelling. The upstream miRNAs of GTGs were predicted using corresponding online databases, and the downstream target genes were identified by weighted correlation network analysis (WGCNA). Computer virtual screening and molecular docking predicted potential therapeutic drugs. The identified GTGs were validated in vivo, in vitro and in the human HF-related dataset GSE57338.
Results: Twenty-one differentially expressed GTGs were identified, and these genes were significantly up-regulated in the TAC model except for C1galt1, Extl2 and Pigh. Pearson correlation analysis revealed that 11 GTGs were significantly associated with pathological cardiac remodelling. Fifty-six miRNAs and 31 drugs were predicted to target these GTGs. WGCNA indicated that these GTGs were associated with lipid metabolism-related genes and pathways. Up-regulation of B3gnt9, C1galt1, Gcnt1, Gxylt2 and Mgat5b was observed in the TAC model. GXYLT2 is up-regulated and has high disease-predictive value in patients with dilated cardiomyopathy and ischaemic cardiomyopathy. Knockdown of GXYLT2 in human AC16 cardiomyocytes significantly attenuated angiotensin II (AngII)-induced hypertrophy.
Conclusions: Dysregulation of GTG expression may affect TAC-induced HF through metabolic pathways, and GXYLT2 may be a new potential therapeutic target for HF.
期刊介绍：
ESC Heart Failure is the open access journal of the Heart Failure Association of the European Society of Cardiology dedicated to the advancement of knowledge in the field of heart failure. The journal aims to improve the understanding, prevention, investigation and treatment of heart failure. Molecular and cellular biology, pathology, physiology, electrophysiology, pharmacology, as well as the clinical, social and population sciences all form part of the discipline that is heart failure. Accordingly, submission of manuscripts on basic, translational, clinical and population sciences is invited. Original contributions on nursing, care of the elderly, primary care, health economics and other specialist fields related to heart failure are also welcome, as are case reports that highlight interesting aspects of heart failure care and treatment.
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