title: The effect of a preparation of minerals, vitamins and trace elements on the cardiac gene expression pattern in male diabetic rats.
abstract: BACKGROUND
  Diabetic patients have an increased risk of developing cardiovascular diseases, which are the leading cause of death in developed countries. Although multivitamin products are widely used as dietary supplements, the effects of these products have not been investigated in the diabetic heart yet. Therefore, here we investigated if a preparation of different minerals, vitamins, and trace elements (MVT) affects the cardiac gene expression pattern in experimental diabetes.
  
  
  METHODS
  Two-day old male Wistar rats were injected with streptozotocin (i.p. 100 mg/kg) or citrate buffer to induce diabetes. From weeks 4 to 12, rats were fed with a vehicle or a MVT preparation. Fasting blood glucose measurement and oral glucose tolerance test were performed at week 12, and then total RNA was isolated from the myocardium and assayed by rat oligonucleotide microarray for 41012 oligonucleotides.
  
  
  RESULTS
  Significantly elevated fasting blood glucose concentration and impaired glucose tolerance were markedly improved by MVT-treatment in diabetic rats at week 12. Genes with significantly altered expression due to diabetes include functional clusters related to cardiac hypertrophy (e.g. caspase recruitment domain family, member 9; cytochrome P450, family 26, subfamily B, polypeptide; FXYD domain containing ion transport regulator 3), stress response (e.g. metallothionein 1a; metallothionein 2a; interleukin-6 receptor; heme oxygenase (decycling) 1; and glutathione S-transferase, theta 3), and hormones associated with insulin resistance (e.g. resistin; FK506 binding protein 5; galanin/GMAP prepropeptide). Moreover the expression of some other genes with no definite cardiac function was also changed such as e.g. similar to apolipoprotein L2; brain expressed X-linked 1; prostaglandin b2 synthase (brain). MVT-treatment in diabetic rats showed opposite gene expression changes in the cases of 19 genes associated with diabetic cardiomyopathy. In healthy hearts, MVT-treatment resulted in cardiac gene expression changes mostly related to immune response (e.g. complement factor B; complement component 4a; interferon regulatory factor 7; hepcidin).
  
  
  CONCLUSIONS
  MVT-treatment improved diagnostic markers of diabetes. This is the first demonstration that MVT-treatment significantly alters cardiac gene expression profile in both control and diabetic rats. Our results and further studies exploring the mechanistic role of individual genes may contribute to the prevention or diagnosis of cardiac complications in diabetes.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, University of Szeged, Szeged, Hungary. sarkozy.marta@med.u-szeged.hu.
authors.forename: Márta
authors.initials: M
authors.lastname: Sárközy
authors.affiliation: Department of Biochemistry, Faculty of Medicine, University of Szeged, Szeged, Hungary. szucs.gergo@med.u-szeged.hu.
authors.forename: Gergő
authors.initials: G
authors.lastname: Szűcs
authors.affiliation: Department of Biochemistry, Faculty of Medicine, University of Szeged, Szeged, Hungary. pipicz.marton@med.u-szeged.hu.
authors.forename: Márton
authors.initials: M
authors.lastname: Pipicz
authors.affiliation: Institute of Genetics, Biological Research Center of the Hungarian Academy of Sciences, Szeged, Hungary. zvara.agnes@brc.mta.hu.
authors.forename: Ágnes
authors.initials: Á
authors.lastname: Zvara
authors.affiliation: Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary. ederkati@gmail.com.
authors.forename: Katalin
authors.initials: K
authors.lastname: Éder
authors.affiliation: Department of Biochemistry, Faculty of Medicine, University of Szeged, Szeged, Hungary. veronikafeketedr@gmail.com.
authors.forename: Veronika
authors.initials: V
authors.lastname: Fekete
authors.affiliation: Béres Pharmaceuticals Ltd, Budapest, Hungary. szucs.csilla@beres.hu.
authors.forename: Csilla
authors.initials: C
authors.lastname: Szűcs
authors.affiliation: Béres Pharmaceuticals Ltd, Budapest, Hungary. barkanyi.judit@beres.hu.
authors.forename: Judit
authors.initials: J
authors.lastname: Bárkányi
authors.affiliation: Department of Biochemistry, Faculty of Medicine, University of Szeged, Szeged, Hungary. csonka.csaba@med.u-szeged.hu.
authors.forename: Csaba
authors.initials: C
authors.lastname: Csonka
authors.affiliation: Institute of Genetics, Biological Research Center of the Hungarian Academy of Sciences, Szeged, Hungary. puskas.laszlo@brc.mta.hu.
authors.forename: László G
authors.initials: LG
authors.lastname: Puskás
authors.affiliation: Béres Pharmaceuticals Ltd, Budapest, Hungary. konya.csaba@beres.hu.
authors.forename: Csaba
authors.initials: C
authors.lastname: Kónya
authors.affiliation: Pharmahungary Group, Szeged, Hungary. peter.ferdinandy@pharmahungary.com.|Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary. peter.ferdinandy@pharmahungary.com.
authors.forename: Péter
authors.initials: P
authors.lastname: Ferdinandy
authors.affiliation: Department of Biochemistry, Faculty of Medicine, University of Szeged, Szeged, Hungary. csont.tamas@med.u-szeged.hu.
authors.forename: Tamás
authors.initials: T
authors.lastname: Csont
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000235:genetics*; D058065:Diabetic Cardiomyopathies / Q000235:genetics*; D006321:Heart / Q000187:drug effects*; D008297:Male; D008903:Minerals / Q000494:pharmacology*; D009206:Myocardium / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014131:Trace Elements / Q000494:pharmacology*; D059467:Transcriptome / Q000187:drug effects*; D014815:Vitamins / Q000494:pharmacology*
chemical_list: D008903:Minerals; D012333:RNA, Messenger; D014131:Trace Elements; D014815:Vitamins