Effects of Levosimendan on Cardiac Gene Expression Profile and Post‐Infarct Cardiac Remodelling in Diabetic Goto‐Kakizaki Rats

摘要: Abstract:  The calcium sensitizer levosimendan has shown beneficial effects on cardiac remodelling in spontaneously diabetic Goto-Kakizaki (GK) rats 12 weeks after experimental myocardial infarction (MI). However, the short-term and cellular mechanisms remain partially unresolved. aim was to study of oral treatment gene expression profile GK 4 weeks MI/sham operation. MI induced rats. Twenty-four hours surgery, were randomized into four groups: MI, +levosimendan (1 mg/kg/day), sham-operated +levosimendan. Cardiac function histology examined 1, 4 MI. investigated by microarray analysis. Levosimendan ameliorated post-infarct heart failure remodelling. altered 264 sham rats, respectively; these changes associated with alterations two Kyoto Encyclopedia Genes Genomes (KEGG) pathways. up-regulated 3 genes renin-angiotensin system pathway [angiotensin receptor 1 (Agtr1), chymase (Cma1) thimet oligopeptidase (Thop1)] down-regulated glycerolipid metabolism [diacylglycerol kinase gamma (Dgkg), carboxyl ester lipase (Cel) Diacylglycerol iota]. opposite pleckstrin homology (PH) domain?containing family f (Plekhf1), carboxymethylenebutenolidase homologue (Cmbl) (up-regulation) hydroxyprostaglandin dehydrogenase 15 (Hpgd) (down-regulation) as compared versus affected 420 12 KEGG hypertrophy 522 three pathways including purine metabolism, cell cycle cancer. protects against Analysis transcriptome revealed several that are regulated levosimendan. These may represent novel drug targets for cardiomyopathy.