title: Severe pulmonary hypertension is associated with altered right ventricle metabolic substrate uptake.
abstract: In severe pulmonary hypertension (SPH), prior studies have shown an increase in right ventricle (RV) uptake of glucose, but it is unclear whether there is a change in the relative utilization of fatty acids. We hypothesized that in the RV in SPH, as in left ventricular (LV) failure, there is altered substrate utilization, with increased glucose uptake and decreased fatty acid uptake. SPH was induced in rats by treatment with the VEGF receptor inhibitor SU5416 and 3 wk of hypoxia (10% FiO2 ), followed by an additional 4 wk of normoxia (SU-Hx group). Control rats were treated with carboxymethylcellulose vehicle and 7 wk of normoxia (CMC-Nx group). The rodents then underwent positron emission tomography with sequential administration of two radiotracers, 2-deoxy-2-[(18)F]fluoroglucose ((18)F-FDG) and 14-(R,S)-[(18)F]fluoro-6-thia-heptadecanoic acid ((18)F-FTHA), analogs of glucose and fatty acid, respectively. Five CMC-Nx and 3 SU-Hx rats completed the entire experimental protocol. In the RV, there was a mild increase in (18)F-FDG uptake (1.35-fold, P = 0.085) and a significant decrease in (18)F-FTHA uptake (-2.1-fold, P < 0.05) in the SU-Hx rats relative to the CMC-Nx rats. In the LV, SU-Hx rats had less uptake of both radiotracers compared with CMC-Nx rats. Less RV fatty acid uptake in SPH was corroborated by decreased fatty acid transporters and enzymes in the RV tissue, and specifically a decrease in lipoprotein lipase. In the RV in rats with SPH, there is a major shift in metabolic substrate preference, largely due to decreased fatty acid uptake.
authors.affiliation: Department of Medicine, University of Colorado Denver, Aurora, Colorado; brian.graham@ucdenver.edu.
authors.forename: Brian B
authors.initials: BB
authors.lastname: Graham
authors.affiliation: Department of Medicine, University of Colorado Denver, Aurora, Colorado;
authors.forename: Rahul
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Department of Medicine, University of Colorado Denver, Aurora, Colorado;
authors.forename: Claudia
authors.initials: C
authors.lastname: Mickael
authors.affiliation: Department of Medicine, University of Colorado Denver, Aurora, Colorado;
authors.forename: Linda
authors.initials: L
authors.lastname: Sanders
authors.affiliation: Department of Medicine, University of Colorado Denver, Aurora, Colorado;
authors.forename: Liya
authors.initials: L
authors.lastname: Gebreab
authors.affiliation: Department of Anesthesiology, University of Colorado Denver, Aurora, Colorado; and.
authors.forename: Kendra M
authors.initials: KM
authors.lastname: Huber
authors.affiliation: Department of Medicine, University of Colorado Denver, Aurora, Colorado;
authors.forename: Mario
authors.initials: M
authors.lastname: Perez
authors.affiliation: Department of Psychiatry, Stony Brook School of Medicine, Stony Brook, New York.
authors.forename: Peter
authors.initials: P
authors.lastname: Smith-Jones
authors.affiliation: Department of Anesthesiology, University of Colorado Denver, Aurora, Colorado; and.
authors.forename: Natalie J
authors.initials: NJ
authors.lastname: Serkova
authors.affiliation: Department of Medicine, University of Colorado Denver, Aurora, Colorado;
authors.forename: Rubin M
authors.initials: RM
authors.lastname: Tuder
mesh_terms: D000818:Animals; D001692:Biological Transport; D050612:Fatty Acid Transport Proteins / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006352:Heart Ventricles / Q000378:metabolism* / Q000503:physiopathology*; D006976:Hypertension, Pulmonary / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D007211:Indoles / Q000494:pharmacology; D008071:Lipoprotein Lipase / Q000378:metabolism; D010084:Oxidation-Reduction; D049268:Positron-Emission Tomography; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D019275:Radiopharmaceuticals; D051381:Rats; D017207:Rats, Sprague-Dawley; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors
chemical_list: D050612:Fatty Acid Transport Proteins; D005227:Fatty Acids; D007211:Indoles; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D019275:Radiopharmaceuticals; C116890:Semaxinib; D040262:Receptors, Vascular Endothelial Growth Factor; D008071:Lipoprotein Lipase; D005947:Glucose
keywords: fatty acid oxidation; metabolism; pulmonary hypertension; right ventricle