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Network Analyses Links Epicardial Fat Metabolism to Human Coronary Heart Disease

37 Pages Posted: 16 Apr 2021 Publication Status: Review Complete

See all articles by Stephen Doran

Stephen Doran

King's College London - Centre for Host-Microbiome Interactions

Muhammad Arif

Royal Institute of Technology (KTH) - Science for Life Laboratory

Maryam Clausen

AstraZeneca Pharmaceuticals - IMED Biotech Unit

Johannes Wikström

AstraZeneca Pharmaceuticals - Bioscience Metabolism, Research and Early Development Cardiovascular, Renal and Metabolism (CVRM)

Mohammad Bohlooly-Y

AstraZeneca Pharmaceuticals - IMED Biotech Unit

Anders Jeppsson

University of Gothenburg - Department of Molecular and Clinical Medicine

Malin Levin

University of Gothenburg - Department of Molecular and Clinical Medicine

Adil Mardinoglu

Royal Institute of Technology (KTH) - Science for Life Laboratory

Jan Boren

University of Gothenburg - Department of Molecular and Clinical Medicine

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Abstract

The generation of tissue-specific integrated networks (INs) through the merging of transcriptional regulatory, protein-protein interaction and genome-scale metabolic networks allows for a rigorous investigation of the biological processes that are altered in cardiovascular disease (CVD) subjects. We developed INs for left ventricle (LV) and visceral adipose tissue (omentum) of healthy subjects and compared these with LV and epicardial fat INs for CVD subjects. We investigated changes in co-regulation for enzymes in pathways that are known to be associated with the development and progression of CVD for each tissue type. Global gene expression changes between healthy and CVD subjects were determined for both tissue types and reporter metabolite analyses were performed. The application and combination of these different network approaches enabled us to associate low levels of Coenzyme Q10 with cardiac remodelling in the LV. We also found increasing homocysteine levels with dysregulation of the adipocytokine pathway in the epicardial fat of CVD subjects and validated our predictions by detecting increased plasma metabolite levels associated with homocysteine in CVD subjects.

Suggested Citation

Doran, Stephen and Arif, Muhammad and Clausen, Maryam and Wikström, Johannes and Bohlooly-Y, Mohammad and Jeppsson, Anders and Levin, Malin and Mardinoglu, Adil and Boren, Jan, Network Analyses Links Epicardial Fat Metabolism to Human Coronary Heart Disease. Available at SSRN: https://ssrn.com/abstract=3828226 or http://dx.doi.org/10.2139/ssrn.3828226
This version of the paper has not been formally peer reviewed.

Stephen Doran (Contact Author)

King's College London - Centre for Host-Microbiome Interactions ( email )

United Kingdom

Muhammad Arif

Royal Institute of Technology (KTH) - Science for Life Laboratory ( email )

Stockholm, SE-100 44
Sweden

Maryam Clausen

AstraZeneca Pharmaceuticals - IMED Biotech Unit

Mölndal
Sweden

Johannes Wikström

AstraZeneca Pharmaceuticals - Bioscience Metabolism, Research and Early Development Cardiovascular, Renal and Metabolism (CVRM) ( email )

Gothenburg
Sweden

Mohammad Bohlooly-Y

AstraZeneca Pharmaceuticals - IMED Biotech Unit ( email )

Mölndal
Sweden
+46-31-7064181 (Phone)

Anders Jeppsson

University of Gothenburg - Department of Molecular and Clinical Medicine ( email )

Gothenburg
Sweden

Malin Levin

University of Gothenburg - Department of Molecular and Clinical Medicine ( email )

Gothenburg
Sweden

Adil Mardinoglu

Royal Institute of Technology (KTH) - Science for Life Laboratory ( email )

Stockholm, SE-100 44
Sweden

Jan Boren

University of Gothenburg - Department of Molecular and Clinical Medicine ( email )

PO Box 400
Göteborg, SE405 30
Sweden

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