학술논문
Unraveling the Metabolic Derangements Occurring in Non-infarcted Areas of Pig Hearts With Chronic Heart Failure.
Document Type
Academic Journal
Author
Correia C; Systems Biology Research Center, Translational Bioinformatics Research Group, School of Biosciences, University of Skövde, Skövde, Sweden.; Bioscience Cardiovascular, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.; Wang QD; Bioscience Cardiovascular, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.; Linhardt G; Bioscience Cardiovascular, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.; Carlsson LG; Bioscience Cardiovascular, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.; Ulfenborg B; Systems Biology Research Center, Translational Bioinformatics Research Group, School of Biosciences, University of Skövde, Skövde, Sweden.; Walentinsson A; Translational Science & Experimental Medicine, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.; Rydén-Markinhutha K; Bioscience Cardiovascular, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.; Behrendt M; Bioscience Cardiovascular, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.; Wikström J; Bioscience Cardiovascular, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.; Sartipy P; Systems Biology Research Center, Translational Bioinformatics Research Group, School of Biosciences, University of Skövde, Skövde, Sweden.; Late-Stage Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.; Jennbacken K; Bioscience Cardiovascular, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.; Synnergren J; Systems Biology Research Center, Translational Bioinformatics Research Group, School of Biosciences, University of Skövde, Skövde, Sweden.
Source
Publisher: Frontiers Media S.A Country of Publication: Switzerland NLM ID: 101653388 Publication Model: eCollection Cited Medium: Print ISSN: 2297-055X (Print) Linking ISSN: 2297055X NLM ISO Abbreviation: Front Cardiovasc Med Subsets: PubMed not MEDLINE
Subject
Language
English
ISSN
2297-055X
Abstract
Objective: After myocardial infarction (MI), the non-infarcted left ventricle (LV) ensures appropriate contractile function of the heart. Metabolic disturbance in this region greatly exacerbates post-MI heart failure (HF) pathology. This study aimed to provide a comprehensive understanding of the metabolic derangements occurring in the non-infarcted LV that could trigger cardiovascular deterioration. Methods and Results: We used a pig model that progressed into chronic HF over 3 months following MI induction. Integrated gene and metabolite signatures revealed region-specific perturbations in amino acid- and lipid metabolism, insulin signaling and, oxidative stress response. Remote LV, in particular, showed impaired glutamine and arginine metabolism, altered synthesis of lipids, glucose metabolism disorder, and increased insulin resistance. LPIN1, PPP1R3C, PTPN1, CREM , and NR0B2 were identified as the main effectors in metabolism dysregulation in the remote zone and were found differentially expressed also in the myocardium of patients with ischemic and/or dilated cardiomyopathy. In addition, a simultaneous significant decrease in arginine levels and altered PRCP, PTPN1 , and ARF6 expression suggest alterations in vascular function in remote area. Conclusions: This study unravels an array of dysregulated genes and metabolites putatively involved in maladaptive metabolic and vascular remodeling in the non-infarcted myocardium and may contribute to the development of more precise therapies to mitigate progression of chronic HF post-MI.
Competing Interests: CC, Q-DW, GL, LC, AW, KR-M, MB, JW, and PS are employed by AstraZeneca. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2021 Correia, Wang, Linhardt, Carlsson, Ulfenborg, Walentinsson, Rydén-Markinhutha, Behrendt, Wikström, Sartipy, Jennbacken and Synnergren.)
Competing Interests: CC, Q-DW, GL, LC, AW, KR-M, MB, JW, and PS are employed by AstraZeneca. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2021 Correia, Wang, Linhardt, Carlsson, Ulfenborg, Walentinsson, Rydén-Markinhutha, Behrendt, Wikström, Sartipy, Jennbacken and Synnergren.)