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

Cardiovascular Diabetology

Original Investigation

Veronika Fekete¹  Gabriella F Kocsis¹  Gergő Szűcs¹  Nóra Gyémánt¹  Márta Sárközy¹  Tamás Csont²  Judit Pipis²  Csaba Csonka²  Ágnes Zvara³  László G Puskás³  Péter Ferdinandy⁴ 

[1] Cardiovascular Research Group, Department of Biochemistry, Faculty of Medicine, University of Szeged, Szeged, Hungary;Cardiovascular Research Group, Department of Biochemistry, Faculty of Medicine, University of Szeged, Szeged, Hungary;Pharmahungary Group, Szeged, Hungary;Department of Functional Genomics, Biological Research Center, Szeged, Hungary;Pharmahungary Group, Szeged, Hungary;Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Budapest, Hungary;

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

DOI  :  10.1186/1475-2840-12-16

 received in 2012-10-14, accepted in 2013-01-05,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundMetabolic 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.MethodsFasting 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.ResultsFasting 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.ConclusionsMetabolic syndrome significantly alters cardiac gene expression profile which may be involved in development of cardiac pathologies in the presence of metabolic syndrome.

【 授权许可】

Unknown   
© Sárközy et al; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.