title: Aliskiren affects fatty-acid uptake and lipid-related genes in rodent and human cardiomyocytes.
abstract: OBJECTIVE
  We investigated whether the direct renin inhibitor aliskiren can affect metabolism in cardiomyocytes from rat, mouse and human sources.
  
  
  RESULTS
  At 10-50 μmol/L, aliskiren significantly increased medium-chain-fatty-acid uptake in primary-cultured neonatal-rat and HL-1 adult-mouse-derived cardiomyocytes (BODIPY-induced fluorescence intensity). The fatty-acid transporter CD-36 was correspondingly translocated to, but the glucose transporter Glut-4 away from, the sarcoplasmic reticulum/plasma membrane, in primary-cultured neonatal-rat (CD-36, Glut-4) and adult-human (CD-36) cardiomyocytes (confocal immunocytochemistry). Immunoblotting showed that aliskiren induced phosphorylation of ERK1/2 in cardiomyocytes from all three sources; responses were dose- and time-dependent, unaffected by renin treatment, and did not cause alterations in expression of (P)R or Igf2/M6P receptors. Microarray analysis of the complete genome of aliskiren-treated neonatal-rat cardiomyocytes, with RT-qPCR and immunoblot confirmation assays in rat and human primary cardiomyocytes, showed that aliskiren up-regulated mRNA and increased protein expression of several enzymes important in lipid and glucose metabolism and in cholesterol biosynthesis. Cardiomyocyte cell-cycle and viability were unaffected by aliskiren.
  
  
  CONCLUSIONS
  Aliskiren can induce changes in fatty-acid and glucose uptake and expression of key enzymes of lipid and cholesterol metabolism, which are not associated with increased expression of (P)R or Igf2/M6P receptors, in cultured cardiomyocytes.
authors.affiliation: Cellular and Molecular Cardiology Research Unit, Department of Cardiology and Institute of Biomedical Research, University Clinical Hospital, Travesı´a Choupana s/n, Santiago de Compostela, Spain.
authors.forename: Diego
authors.initials: D
authors.lastname: Rodríguez-Penas
authors.forename: Sandra
authors.initials: S
authors.lastname: Feijóo-Bandín
authors.forename: Pamela V
authors.initials: PV
authors.lastname: Lear
authors.forename: Ana
authors.initials: A
authors.lastname: Mosquera-Leal
authors.forename: Vanessa
authors.initials: V
authors.lastname: García-Rúa
authors.forename: Manuel F
authors.initials: MF
authors.lastname: Otero
authors.forename: Miguel
authors.initials: M
authors.lastname: Rivera
authors.forename: Oreste
authors.initials: O
authors.lastname: Gualillo
authors.forename: José Ramón
authors.initials: JR
authors.lastname: González-Juanatey
authors.forename: Francisca
authors.initials: F
authors.lastname: Lago
mesh_terms: D000577:Amides / Q000494:pharmacology*; D000818:Animals; D018955:CD36 Antigens / Q000032:analysis; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002784:Cholesterol / Q000096:biosynthesis; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D005650:Fumarates / Q000494:pharmacology*; D051275:Glucose Transporter Type 4 / Q000032:analysis; D006801:Humans; D007850:Lauric Acids / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D017527:Receptor, IGF Type 2 / Q000032:analysis; D000092502:Renin Inhibitors
chemical_list: D000577:Amides; D018955:CD36 Antigens; D002784:Cholesterol; D048049:Extracellular Signal-Regulated MAP Kinases; D005227:Fatty Acids; D005650:Fumarates; D051275:Glucose Transporter Type 4; D007850:Lauric Acids; D017527:Receptor, IGF Type 2; D000092502:Renin Inhibitors; C030358:lauric acid; C446481:aliskiren