title: Expression of retinoic acid target genes in coronary artery disease.
abstract: Coronary atherosclerosis can lead to myocardial infarction, and secondarily to post-infarct remodelling and heart failure. Retinoic acid (RA) influences cell proliferation. We hypothesized that RA could influence gene expression and proliferation of cardiovascular cells. Left ventricular biopsies from patients with end-stage heart failure due to coronary artery disease (CAD) or dilated cardiomyopathy were investigated for the content of RA metabolites using liquid chromatography mass spectrometry (LC-MS/MS), and compared with healthy donors. All-trans retinoic acid (ATRA) was increased in the hearts of CAD patients. Gene expression (quantitative PCR) of RA target genes was not influenced in failing hearts, but was increased in the hearts of patients with CAD undergoing open heart surgery. The expression of RA target genes was increased in atherosclerotic lesions from carotid arteries compared to healthy arteries. Stimulation of cardiomyocytes, cardiofibroblasts, smooth muscle cells and endothelial cells with ATRA increased the gene expression of the key enzymes. Cardiofibroblast and smooth muscle cell proliferation were reduced by ATRA, which increased endothelial cell proliferation. Coronary artery disease leads to increased expression of RA target genes. ATRA accumulated in the failing human heart. All investigated cell types present in the heart had induced expression of RA target genes when stimulated with ATRA, which also influenced cell proliferation.
authors.affiliation: Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors.forename: Dusan
authors.initials: D
authors.lastname: Bilbija
authors.affiliation: Department of Clinical Medicine, School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
authors.forename: Ali Ateia
authors.initials: AA
authors.lastname: Elmabsout
authors.affiliation: Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors.forename: Julia
authors.initials: J
authors.lastname: Sagave
authors.affiliation: Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors.forename: Fred
authors.initials: F
authors.lastname: Haugen
authors.affiliation: Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors.forename: Nasser
authors.initials: N
authors.lastname: Bastani
authors.affiliation: Center for Heart Failure Research, University of Oslo, Oslo, Norway.
authors.forename: Christen Peder
authors.initials: CP
authors.lastname: Dahl
authors.affiliation: Center for Heart Failure Research, University of Oslo, Oslo, Norway.
authors.forename: Lars
authors.initials: L
authors.lastname: Gullestad
authors.affiliation: Department of Clinical Medicine, School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
authors.forename: Allan
authors.initials: A
authors.lastname: Sirsjö
authors.affiliation: Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors.forename: Rune
authors.initials: R
authors.lastname: Blomhoff
authors.affiliation: Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors.forename: Guro
authors.initials: G
authors.lastname: Valen
mesh_terms: D001706:Biopsy; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003324:Coronary Artery Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005347:Fibroblasts / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006352:Heart Ventricles / Q000378:metabolism; D006801:Humans; D009203:Myocardial Infarction / Q000235:genetics* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects; D018168:Receptors, Retinoic Acid / Q000096:biosynthesis* / Q000235:genetics; D053719:Tandem Mass Spectrometry; D014212:Tretinoin / Q000008:administration & dosage*
chemical_list: D018168:Receptors, Retinoic Acid; D014212:Tretinoin