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Open Access Original investigation

Metabolic syndrome influences cardiac gene expression pattern at the transcript level in male ZDF rats

Márta Sárközy1, Ágnes Zvara2, Nóra Gyémánt1, Veronika Fekete1, Gabriella F Kocsis1, Judit Pipis13, Gergő Szűcs1, Csaba Csonka13, László G Puskás2, Péter Ferdinandy34 and Tamás Csont13*

Author Affiliations

1 Cardiovascular Research Group, Department of Biochemistry, Faculty of Medicine, University of Szeged, Szeged, Hungary

2 Department of Functional Genomics, Biological Research Center, Szeged, Hungary

3 Pharmahungary Group, Szeged, Hungary

4 Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Budapest, Hungary

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Cardiovascular Diabetology 2013, 12:16  doi:10.1186/1475-2840-12-16

Published: 15 January 2013

Abstract

Background

Metabolic syndrome (coexisting visceral obesity, dyslipidemia, hyperglycemia, and hypertension) is a prominent risk factor for cardiovascular morbidity and mortality, however, its effect on cardiac gene expression pattern is unclear. Therefore, we examined the possible alterations in cardiac gene expression pattern in male Zucker Diabetic Fatty (ZDF) rats, a model of metabolic syndrome.

Methods

Fasting blood glucose, serum insulin, cholesterol and triglyceride levels were measured at 6, 16, and 25 wk of age in male ZDF and lean control rats. Oral glucose tolerance test was performed at 16 and 25 wk of age. At week 25, total RNA was isolated from the myocardium and assayed by rat oligonucleotide microarray for 14921 genes. Expression of selected genes was confirmed by qRT-PCR.

Results

Fasting blood glucose, serum insulin, cholesterol and triglyceride levels were significantly increased, glucose tolerance and insulin sensitivity were impaired in ZDF rats compared to leans. In hearts of ZDF rats, 36 genes showed significant up-regulation and 49 genes showed down-regulation as compared to lean controls. Genes with significantly altered expression in the heart due to metabolic syndrome includes functional clusters of metabolism (e.g. 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 2; argininosuccinate synthetase; 2-amino-3-ketobutyrate-coenzyme A ligase), structural proteins (e.g. myosin IXA; aggrecan1), signal transduction (e.g. activating transcription factor 3; phospholipase A2; insulin responsive sequence DNA binding protein-1) stress response (e.g. heat shock 70kD protein 1A; heat shock protein 60; glutathione S-transferase Yc2 subunit), ion channels and receptors (e.g. ATPase, (Na+)/K+ transporting, beta 4 polypeptide; ATPase, H+/K+ transporting, nongastric, alpha polypeptide). Moreover some other genes with no definite functional clusters were also changed such as e.g. S100 calcium binding protein A3; ubiquitin carboxy-terminal hydrolase L1; interleukin 18. Gene ontology analysis revealed several significantly enriched functional inter-relationships between genes influenced by metabolic syndrome.

Conclusions

Metabolic syndrome significantly alters cardiac gene expression profile which may be involved in development of cardiac pathologies in the presence of metabolic syndrome.

Keywords:
Metabolic syndrome; Diabetes mellitus type 2; Hyperlipidemia; Myocardium; DNA microarray; Heart; GO analysis