Molecular characterızatıon of wnt/b-catenın sıgnalıng pathway after myocardıal infarctıon

2. SUMMARYMOLECULAR CHARACTERIZATION OF WNT/B-CATENIN SIGNALINGPATHWAY AFTER MYOCARDIAL INFARCTIONDr. Emel Fermanci, Dokuz Eylül University Faculty of Medicine Department ofCardiovascular Surgery, Izmir, Turkey.(efermanci@deu.edu.tr)OBJECTIVES: Myocardial infarction induces global changes in the ventricular architecture, aprocess called ventricular remodeling. Molecular mechanism behind this process still is notclearly identified. Since Wnt/ß-catenin signaling pathway involves in a variety of modeling andremodeling processes including cell proliferation, differentiation, apoptosis and the control ofcell orientation. We assume that alterations in this pathway may be one of the mechanismexplaining immediate response in infarct and remote zone after acute myocardial infarction.Aim of our study is to show changing in gene expression at ischemic and non-ischemicmyocardial tissues and also finding possible target molecules for treatment strategies.METHODS: Myocardial infarction was produced by coronary artery ligation of Wistar rats.Animals were divided into two groups. Sham operation comprised surgical procedure withoutligature placement. Following thirty minutes after operation, all animals were sacrificed, heartswere dissected and myocardial samples were obtained from remote and infarct zones. Tissuesamples were immediately flash-frozen for RNA analysis. Total RNA was extracted andreverse transcribed. Aliquots of cDNA?s were then amplified with oligonucleotide primersspesific for the target genes by semi-quantitative RT-PCR. Histopathological analysis wasestablished on tissue samples to verify presence of ischemia in infarct zone.FINDINGS: Optimization of the RT-PCR amplifications from Wnt1, Wnt3a, Wnt5a, Wnt9a,axin, ß-catenin, secreted Frizzled Related Protein (sFRP1), Dishelleved, Frz2, Frz4 and Frz6genes were performed, differential expression of genes which have roles in the Wnt signalingwere presented in. When expression of genes have been compared between both groups oftissues taken from separate animals with and/or without LAD ligation, there were differencefor the levels of Frz2 and sFRP1 transcription under the effect of ischemia caused by ligation.RESULT: SFrz1 and Axin which regulates cytoplasmic level of ß-catenin proteins are knownas secreted activators or inhibitors of Wnt signaling therefore ischemia occurred by the MI inrats regulate expression of these genes in order to give quick response for protectingmyocardial cells.Key Words: Acute MI, Wnt-ß catenin signaling pathway, Frz2 and sFRP1.