Retinoic acid signalling is activated in the postischemic heart and may influence remodelling

• Published in: PloS one 2012-09, Vol.7 (9), p.e44740-e44740
• Main Authors: Bilbija, Dusan, Haugen, Fred, Sagave, Julia, Baysa, Anton, Bastani, Nasser, Levy, Finn Olav, Sirsjö, Allan, Blomhoff, Rune, Valen, Guro
• Format: Article
• Language: English
• Subjects: Acids; Activation; Aldehyde dehydrogenase; Animals; Biochemistry; Biology; Cancer; Cardiomyocytes; Cardiomyopathy; Cardiovascular disease; Cell differentiation; Cell Research; Cellforskning; Cellular signal transduction; Chromatography; Clinical medicine; Coronary artery; Coronary vessels; Cytochrome; Cytochrome P450; Enzymes; Experiments; Gene expression; Genes; Heart; Heart attacks; Heart diseases; Heart failure; Hypoxia-Inducible Factor 1 - antagonists & inhibitors; Hypoxia-Inducible Factor 1 - metabolism; Infarction; Ischemia; Kinases; Leukemia; Liquid chromatography; Male; Mass spectrometry; Mass spectroscopy; Medicin; Medicine; Metabolites; Mice; Mice, Inbred C57BL; Morphogenesis; Mustard Compounds - pharmacology; Myocardial infarction; Myocardial Infarction - metabolism; Myocardial ischemia; Myocytes, Cardiac - cytology; Myocytes, Cardiac - drug effects; Ostomy; Phenylpropionates - pharmacology; Physiology; Polymerase chain reaction; Proteins; Receptors; Receptors, Retinoic Acid - genetics; Receptors, Retinoic Acid - metabolism; Regulatory sequences; Remodeling; Retinoic acid; Retinoic acid receptors; Retinoids; Retinoids - metabolism; Ribonucleic acid; RNA; Rodents; Scientific imaging; Signal transduction; Signal Transduction - drug effects; Signaling; Thorax; Transcription activation; Tretinoin; Tretinoin - pharmacology; Vitamin A
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0044740

All-trans retinoic acid (atRA), an active derivative of vitamin A, regulates cell differentiation, proliferation and cardiac morphogenesis via transcriptional activation of retinoic acid receptors (RARs) acting on retinoic acid response elements (RARE). We hypothesized that the retinoic acid (RA) signalling pathway is activated in myocardial ischemia and postischemic remodelling. Myocardial infarction was induced through ligating the left coronary artery in mice. In vivo cardiac activation of the RARs was measured by imaging RARE-luciferase reporter mice, and analysing expression of RAR target genes and proteins by real time RT-PCR and western blot. Endogenous retinoids in postinfarcted hearts were analysed by triple-stage liquid chromatography/tandem mass spectrometry. Cardiomyocytes (CM) and cardiofibroblasts (CF) were isolated from infarcted and sham operated RARE luciferase reporter hearts and monitored for RAR activity and expression of target genes. The effect of atRA on CF proliferation was evaluated by EdU incorporation. Myocardial infarction increased thoracic RAR activity in vivo (p