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Metabolic Reprogramming Regulates the Proliferative and Inflammatory Phenotype of Adventitial Fibroblasts in Pulmonary Hypertension Through the Transcriptional Corepressor C-Terminal Binding Protein-1

Li, Min
Autor Li, Min From Cardiovascular Pulmonary Research Laboratories, Department of Pediatrics and Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO (M.L., S.R., H.Z., A.F., B.A.M., M.F., S.K., M.A.F., K.R.S.); Department of Biochemistry and Molecular Genetics and Biological Mass Spectrometry Shared Resource (A.D., K.C.H.), Department of Anesthesiology (N.J.S.), Advanced Light Microscopy Core Facility (R.M.), Department of Dermatology (H.L., H.L., Q.Z.), and Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition (K.C.E.K.), University of Colorado, Denver; Department of Mitochondrial Physiology, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic (L.P.-H., P.J.); Department of Lung Development and Remodeling, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany (D.I., S.P.); Center for Genetic Improvement of Livestock, Department of Animal Bioscience, University of Guelph, Guelph, ON, Canada (A.C.); Department of Animal Science, University of California-Davis, Davis (J.F.M.); and Department of Animal Science, Colorado State University, Fort Collins (M.G.T.)
Riddle, Suzette
Autor Riddle, Suzette From Cardiovascular Pulmonary Research Laboratories, Department of Pediatrics and Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO (M.L., S.R., H.Z., A.F., B.A.M., M.F., S.K., M.A.F., K.R.S.); Department of Biochemistry and Molecular Genetics and Biological Mass Spectrometry Shared Resource (A.D., K.C.H.), Department of Anesthesiology (N.J.S.), Advanced Light Microscopy Core Facility (R.M.), Department of Dermatology (H.L., H.L., Q.Z.), and Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition (K.C.E.K.), University of Colorado, Denver; Department of Mitochondrial Physiology, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic (L.P.-H., P.J.); Department of Lung Development and Remodeling, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany (D.I., S.P.); Center for Genetic Improvement of Livestock, Department of Animal Bioscience, University of Guelph, Guelph, ON, Canada (A.C.); Department of Animal Science, University of California-Davis, Davis (J.F.M.); and Department of Animal Science, Colorado State University, Fort Collins (M.G.T.)
Zhang, Hui
Autor Zhang, Hui From Cardiovascular Pulmonary Research Laboratories, Department of Pediatrics and Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO (M.L., S.R., H.Z., A.F., B.A.M., M.F., S.K., M.A.F., K.R.S.); Department of Biochemistry and Molecular Genetics and Biological Mass Spectrometry Shared Resource (A.D., K.C.H.), Department of Anesthesiology (N.J.S.), Advanced Light Microscopy Core Facility (R.M.), Department of Dermatology (H.L., H.L., Q.Z.), and Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition (K.C.E.K.), University of Colorado, Denver; Department of Mitochondrial Physiology, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic (L.P.-H., P.J.); Department of Lung Development and Remodeling, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany (D.I., S.P.); Center for Genetic Improvement of Livestock, Department of Animal Bioscience, University of Guelph, Guelph, ON, Canada (A.C.); Department of Animal Science, University of California-Davis, Davis (J.F.M.); and Department of Animal Science, Colorado State University, Fort Collins (M.G.T.)
D'Alessandro, Angelo
Autor D'Alessandro, Angelo From Cardiovascular Pulmonary Research Laboratories, Department of Pediatrics and Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO (M.L., S.R., H.Z., A.F., B.A.M., M.F., S.K., M.A.F., K.R.S.); Department of Biochemistry and Molecular Genetics and Biological Mass Spectrometry Shared Resource (A.D., K.C.H.), Department of Anesthesiology (N.J.S.), Advanced Light Microscopy Core Facility (R.M.), Department of Dermatology (H.L., H.L., Q.Z.), and Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition (K.C.E.K.), University of Colorado, Denver; Department of Mitochondrial Physiology, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic (L.P.-H., P.J.); Department of Lung Development and Remodeling, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany (D.I., S.P.); Center for Genetic Improvement of Livestock, Department of Animal Bioscience, University of Guelph, Guelph, ON, Canada (A.C.); Department of Animal Science, University of California-Davis, Davis (J.F.M.); and Department of Animal Science, Colorado State University, Fort Collins (M.G.T.)
Flockton, Amanda
Autor Flockton, Amanda From Cardiovascular Pulmonary Research Laboratories, Department of Pediatrics and Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO (M.L., S.R., H.Z., A.F., B.A.M., M.F., S.K., M.A.F., K.R.S.); Department of Biochemistry and Molecular Genetics and Biological Mass Spectrometry Shared Resource (A.D., K.C.H.), Department of Anesthesiology (N.J.S.), Advanced Light Microscopy Core Facility (R.M.), Department of Dermatology (H.L., H.L., Q.Z.), and Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition (K.C.E.K.), University of Colorado, Denver; Department of Mitochondrial Physiology, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic (L.P.-H., P.J.); Department of Lung Development and Remodeling, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany (D.I., S.P.); Center for Genetic Improvement of Livestock, Department of Animal Bioscience, University of Guelph, Guelph, ON, Canada (A.C.); Department of Animal Science, University of California-Davis, Davis (J.F.M.); and Department of Animal Science, Colorado State University, Fort Collins (M.G.T.)
Serkova, Natalie J
Autor Serkova, Natalie J From Cardiovascular Pulmonary Research Laboratories, Department of Pediatrics and Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO (M.L., S.R., H.Z., A.F., B.A.M., M.F., S.K., M.A.F., K.R.S.); Department of Biochemistry and Molecular Genetics and Biological Mass Spectrometry Shared Resource (A.D., K.C.H.), Department of Anesthesiology (N.J.S.), Advanced Light Microscopy Core Facility (R.M.), Department of Dermatology (H.L., H.L., Q.Z.), and Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition (K.C.E.K.), University of Colorado, Denver; Department of Mitochondrial Physiology, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic (L.P.-H., P.J.); Department of Lung Development and Remodeling, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany (D.I., S.P.); Center for Genetic Improvement of Livestock, Department of Animal Bioscience, University of Guelph, Guelph, ON, Canada (A.C.); Department of Animal Science, University of California-Davis, Davis (J.F.M.); and Department of Animal Science, Colorado State University, Fort Collins (M.G.T.)
Hansen, Kirk C
Autor Hansen, Kirk C From Cardiovascular Pulmonary Research Laboratories, Department of Pediatrics and Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO (M.L., S.R., H.Z., A.F., B.A.M., M.F., S.K., M.A.F., K.R.S.); Department of Biochemistry and Molecular Genetics and Biological Mass Spectrometry Shared Resource (A.D., K.C.H.), Department of Anesthesiology (N.J.S.), Advanced Light Microscopy Core Facility (R.M.), Department of Dermatology (H.L., H.L., Q.Z.), and Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition (K.C.E.K.), University of Colorado, Denver; Department of Mitochondrial Physiology, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic (L.P.-H., P.J.); Department of Lung Development and Remodeling, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany (D.I., S.P.); Center for Genetic Improvement of Livestock, Department of Animal Bioscience, University of Guelph, Guelph, ON, Canada (A.C.); Department of Animal Science, University of California-Davis, Davis (J.F.M.); and Department of Animal Science, Colorado State University, Fort Collins (M.G.T.)
Moldovan, Radu
Autor Moldovan, Radu From Cardiovascular Pulmonary Research Laboratories, Department of Pediatrics and Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO (M.L., S.R., H.Z., A.F., B.A.M., M.F., S.K., M.A.F., K.R.S.); Department of Biochemistry and Molecular Genetics and Biological Mass Spectrometry Shared Resource (A.D., K.C.H.), Department of Anesthesiology (N.J.S.), Advanced Light Microscopy Core Facility (R.M.), Department of Dermatology (H.L., H.L., Q.Z.), and Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition (K.C.E.K.), University of Colorado, Denver; Department of Mitochondrial Physiology, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic (L.P.-H., P.J.); Department of Lung Development and Remodeling, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany (D.I., S.P.); Center for Genetic Improvement of Livestock, Department of Animal Bioscience, University of Guelph, Guelph, ON, Canada (A.C.); Department of Animal Science, University of California-Davis, Davis (J.F.M.); and Department of Animal Science, Colorado State University, Fort Collins (M.G.T.)
McKeon, B Alexandre
Autor McKeon, B Alexandre From Cardiovascular Pulmonary Research Laboratories, Department of Pediatrics and Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO (M.L., S.R., H.Z., A.F., B.A.M., M.F., S.K., M.A.F., K.R.S.); Department of Biochemistry and Molecular Genetics and Biological Mass Spectrometry Shared Resource (A.D., K.C.H.), Department of Anesthesiology (N.J.S.), Advanced Light Microscopy Core Facility (R.M.), Department of Dermatology (H.L., H.L., Q.Z.), and Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition (K.C.E.K.), University of Colorado, Denver; Department of Mitochondrial Physiology, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic (L.P.-H., P.J.); Department of Lung Development and Remodeling, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany (D.I., S.P.); Center for Genetic Improvement of Livestock, Department of Animal Bioscience, University of Guelph, Guelph, ON, Canada (A.C.); Department of Animal Science, University of California-Davis, Davis (J.F.M.); and Department of Animal Science, Colorado State University, Fort Collins (M.G.T.)
Frid, Maria
Autor Frid, Maria From Cardiovascular Pulmonary Research Laboratories, Department of Pediatrics and Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO (M.L., S.R., H.Z., A.F., B.A.M., M.F., S.K., M.A.F., K.R.S.); Department of Biochemistry and Molecular Genetics and Biological Mass Spectrometry Shared Resource (A.D., K.C.H.), Department of Anesthesiology (N.J.S.), Advanced Light Microscopy Core Facility (R.M.), Department of Dermatology (H.L., H.L., Q.Z.), and Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition (K.C.E.K.), University of Colorado, Denver; Department of Mitochondrial Physiology, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic (L.P.-H., P.J.); Department of Lung Development and Remodeling, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany (D.I., S.P.); Center for Genetic Improvement of Livestock, Department of Animal Bioscience, University of Guelph, Guelph, ON, Canada (A.C.); Department of Animal Science, University of California-Davis, Davis (J.F.M.); and Department of Animal Science, Colorado State University, Fort Collins (M.G.T.)
Kumar, Sushil
Autor Kumar, Sushil From Cardiovascular Pulmonary Research Laboratories, Department of Pediatrics and Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO (M.L., S.R., H.Z., A.F., B.A.M., M.F., S.K., M.A.F., K.R.S.); Department of Biochemistry and Molecular Genetics and Biological Mass Spectrometry Shared Resource (A.D., K.C.H.), Department of Anesthesiology (N.J.S.), Advanced Light Microscopy Core Facility (R.M.), Department of Dermatology (H.L., H.L., Q.Z.), and Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition (K.C.E.K.), University of Colorado, Denver; Department of Mitochondrial Physiology, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic (L.P.-H., P.J.); Department of Lung Development and Remodeling, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany (D.I., S.P.); Center for Genetic Improvement of Livestock, Department of Animal Bioscience, University of Guelph, Guelph, ON, Canada (A.C.); Department of Animal Science, University of California-Davis, Davis (J.F.M.); and Department of Animal Science, Colorado State University, Fort Collins (M.G.T.)
Li, Hong
Autor Li, Hong From Cardiovascular Pulmonary Research Laboratories, Department of Pediatrics and Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO (M.L., S.R., H.Z., A.F., B.A.M., M.F., S.K., M.A.F., K.R.S.); Department of Biochemistry and Molecular Genetics and Biological Mass Spectrometry Shared Resource (A.D., K.C.H.), Department of Anesthesiology (N.J.S.), Advanced Light Microscopy Core Facility (R.M.), Department of Dermatology (H.L., H.L., Q.Z.), and Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition (K.C.E.K.), University of Colorado, Denver; Department of Mitochondrial Physiology, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic (L.P.-H., P.J.); Department of Lung Development and Remodeling, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany (D.I., S.P.); Center for Genetic Improvement of Livestock, Department of Animal Bioscience, University of Guelph, Guelph, ON, Canada (A.C.); Department of Animal Science, University of California-Davis, Davis (J.F.M.); and Department of Animal Science, Colorado State University, Fort Collins (M.G.T.)
Liu, Hongbing
Autor Liu, Hongbing From Cardiovascular Pulmonary Research Laboratories, Department of Pediatrics and Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO (M.L., S.R., H.Z., A.F., B.A.M., M.F., S.K., M.A.F., K.R.S.); Department of Biochemistry and Molecular Genetics and Biological Mass Spectrometry Shared Resource (A.D., K.C.H.), Department of Anesthesiology (N.J.S.), Advanced Light Microscopy Core Facility (R.M.), Department of Dermatology (H.L., H.L., Q.Z.), and Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition (K.C.E.K.), University of Colorado, Denver; Department of Mitochondrial Physiology, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic (L.P.-H., P.J.); Department of Lung Development and Remodeling, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany (D.I., S.P.); Center for Genetic Improvement of Livestock, Department of Animal Bioscience, University of Guelph, Guelph, ON, Canada (A.C.); Department of Animal Science, University of California-Davis, Davis (J.F.M.); and Department of Animal Science, Colorado State University, Fort Collins (M.G.T.)
Caánovas, Angela
Autor Caánovas, Angela From Cardiovascular Pulmonary Research Laboratories, Department of Pediatrics and Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO (M.L., S.R., H.Z., A.F., B.A.M., M.F., S.K., M.A.F., K.R.S.); Department of Biochemistry and Molecular Genetics and Biological Mass Spectrometry Shared Resource (A.D., K.C.H.), Department of Anesthesiology (N.J.S.), Advanced Light Microscopy Core Facility (R.M.), Department of Dermatology (H.L., H.L., Q.Z.), and Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition (K.C.E.K.), University of Colorado, Denver; Department of Mitochondrial Physiology, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic (L.P.-H., P.J.); Department of Lung Development and Remodeling, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany (D.I., S.P.); Center for Genetic Improvement of Livestock, Department of Animal Bioscience, University of Guelph, Guelph, ON, Canada (A.C.); Department of Animal Science, University of California-Davis, Davis (J.F.M.); and Department of Animal Science, Colorado State University, Fort Collins (M.G.T.)
Medrano, Juan F
Autor Medrano, Juan F From Cardiovascular Pulmonary Research Laboratories, Department of Pediatrics and Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO (M.L., S.R., H.Z., A.F., B.A.M., M.F., S.K., M.A.F., K.R.S.); Department of Biochemistry and Molecular Genetics and Biological Mass Spectrometry Shared Resource (A.D., K.C.H.), Department of Anesthesiology (N.J.S.), Advanced Light Microscopy Core Facility (R.M.), Department of Dermatology (H.L., H.L., Q.Z.), and Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition (K.C.E.K.), University of Colorado, Denver; Department of Mitochondrial Physiology, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic (L.P.-H., P.J.); Department of Lung Development and Remodeling, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany (D.I., S.P.); Center for Genetic Improvement of Livestock, Department of Animal Bioscience, University of Guelph, Guelph, ON, Canada (A.C.); Department of Animal Science, University of California-Davis, Davis (J.F.M.); and Department of Animal Science, Colorado State University, Fort Collins (M.G.T.)
Thomas, Milton G
Autor Thomas, Milton G From Cardiovascular Pulmonary Research Laboratories, Department of Pediatrics and Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO (M.L., S.R., H.Z., A.F., B.A.M., M.F., S.K., M.A.F., K.R.S.); Department of Biochemistry and Molecular Genetics and Biological Mass Spectrometry Shared Resource (A.D., K.C.H.), Department of Anesthesiology (N.J.S.), Advanced Light Microscopy Core Facility (R.M.), Department of Dermatology (H.L., H.L., Q.Z.), and Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition (K.C.E.K.), University of Colorado, Denver; Department of Mitochondrial Physiology, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic (L.P.-H., P.J.); Department of Lung Development and Remodeling, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany (D.I., S.P.); Center for Genetic Improvement of Livestock, Department of Animal Bioscience, University of Guelph, Guelph, ON, Canada (A.C.); Department of Animal Science, University of California-Davis, Davis (J.F.M.); and Department of Animal Science, Colorado State University, Fort Collins (M.G.T.)
Iloska, Dijana
Autor Iloska, Dijana From Cardiovascular Pulmonary Research Laboratories, Department of Pediatrics and Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO (M.L., S.R., H.Z., A.F., B.A.M., M.F., S.K., M.A.F., K.R.S.); Department of Biochemistry and Molecular Genetics and Biological Mass Spectrometry Shared Resource (A.D., K.C.H.), Department of Anesthesiology (N.J.S.), Advanced Light Microscopy Core Facility (R.M.), Department of Dermatology (H.L., H.L., Q.Z.), and Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition (K.C.E.K.), University of Colorado, Denver; Department of Mitochondrial Physiology, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic (L.P.-H., P.J.); Department of Lung Development and Remodeling, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany (D.I., S.P.); Center for Genetic Improvement of Livestock, Department of Animal Bioscience, University of Guelph, Guelph, ON, Canada (A.C.); Department of Animal Science, University of California-Davis, Davis (J.F.M.); and Department of Animal Science, Colorado State University, Fort Collins (M.G.T.)
Plecitá-Hlavatá, Lydie
Autor Plecitá-Hlavatá, Lydie From Cardiovascular Pulmonary Research Laboratories, Department of Pediatrics and Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO (M.L., S.R., H.Z., A.F., B.A.M., M.F., S.K., M.A.F., K.R.S.); Department of Biochemistry and Molecular Genetics and Biological Mass Spectrometry Shared Resource (A.D., K.C.H.), Department of Anesthesiology (N.J.S.), Advanced Light Microscopy Core Facility (R.M.), Department of Dermatology (H.L., H.L., Q.Z.), and Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition (K.C.E.K.), University of Colorado, Denver; Department of Mitochondrial Physiology, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic (L.P.-H., P.J.); Department of Lung Development and Remodeling, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany (D.I., S.P.); Center for Genetic Improvement of Livestock, Department of Animal Bioscience, University of Guelph, Guelph, ON, Canada (A.C.); Department of Animal Science, University of California-Davis, Davis (J.F.M.); and Department of Animal Science, Colorado State University, Fort Collins (M.G.T.)
Ježek, Petr
Autor Ježek, Petr From Cardiovascular Pulmonary Research Laboratories, Department of Pediatrics and Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO (M.L., S.R., H.Z., A.F., B.A.M., M.F., S.K., M.A.F., K.R.S.); Department of Biochemistry and Molecular Genetics and Biological Mass Spectrometry Shared Resource (A.D., K.C.H.), Department of Anesthesiology (N.J.S.), Advanced Light Microscopy Core Facility (R.M.), Department of Dermatology (H.L., H.L., Q.Z.), and Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition (K.C.E.K.), University of Colorado, Denver; Department of Mitochondrial Physiology, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic (L.P.-H., P.J.); Department of Lung Development and Remodeling, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany (D.I., S.P.); Center for Genetic Improvement of Livestock, Department of Animal Bioscience, University of Guelph, Guelph, ON, Canada (A.C.); Department of Animal Science, University of California-Davis, Davis (J.F.M.); and Department of Animal Science, Colorado State University, Fort Collins (M.G.T.)
Pullamsetti, Soni
Autor Pullamsetti, Soni From Cardiovascular Pulmonary Research Laboratories, Department of Pediatrics and Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO (M.L., S.R., H.Z., A.F., B.A.M., M.F., S.K., M.A.F., K.R.S.); Department of Biochemistry and Molecular Genetics and Biological Mass Spectrometry Shared Resource (A.D., K.C.H.), Department of Anesthesiology (N.J.S.), Advanced Light Microscopy Core Facility (R.M.), Department of Dermatology (H.L., H.L., Q.Z.), and Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition (K.C.E.K.), University of Colorado, Denver; Department of Mitochondrial Physiology, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic (L.P.-H., P.J.); Department of Lung Development and Remodeling, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany (D.I., S.P.); Center for Genetic Improvement of Livestock, Department of Animal Bioscience, University of Guelph, Guelph, ON, Canada (A.C.); Department of Animal Science, University of California-Davis, Davis (J.F.M.); and Department of Animal Science, Colorado State University, Fort Collins (M.G.T.)
Fini, Mehdi A
Autor Fini, Mehdi A From Cardiovascular Pulmonary Research Laboratories, Department of Pediatrics and Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO (M.L., S.R., H.Z., A.F., B.A.M., M.F., S.K., M.A.F., K.R.S.); Department of Biochemistry and Molecular Genetics and Biological Mass Spectrometry Shared Resource (A.D., K.C.H.), Department of Anesthesiology (N.J.S.), Advanced Light Microscopy Core Facility (R.M.), Department of Dermatology (H.L., H.L., Q.Z.), and Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition (K.C.E.K.), University of Colorado, Denver; Department of Mitochondrial Physiology, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic (L.P.-H., P.J.); Department of Lung Development and Remodeling, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany (D.I., S.P.); Center for Genetic Improvement of Livestock, Department of Animal Bioscience, University of Guelph, Guelph, ON, Canada (A.C.); Department of Animal Science, University of California-Davis, Davis (J.F.M.); and Department of Animal Science, Colorado State University, Fort Collins (M.G.T.)
El Kasmi, Karim C
Autor El Kasmi, Karim C From Cardiovascular Pulmonary Research Laboratories, Department of Pediatrics and Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO (M.L., S.R., H.Z., A.F., B.A.M., M.F., S.K., M.A.F., K.R.S.); Department of Biochemistry and Molecular Genetics and Biological Mass Spectrometry Shared Resource (A.D., K.C.H.), Department of Anesthesiology (N.J.S.), Advanced Light Microscopy Core Facility (R.M.), Department of Dermatology (H.L., H.L., Q.Z.), and Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition (K.C.E.K.), University of Colorado, Denver; Department of Mitochondrial Physiology, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic (L.P.-H., P.J.); Department of Lung Development and Remodeling, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany (D.I., S.P.); Center for Genetic Improvement of Livestock, Department of Animal Bioscience, University of Guelph, Guelph, ON, Canada (A.C.); Department of Animal Science, University of California-Davis, Davis (J.F.M.); and Department of Animal Science, Colorado State University, Fort Collins (M.G.T.)
Zhang, QingHong
Autor Zhang, QingHong From Cardiovascular Pulmonary Research Laboratories, Department of Pediatrics and Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO (M.L., S.R., H.Z., A.F., B.A.M., M.F., S.K., M.A.F., K.R.S.); Department of Biochemistry and Molecular Genetics and Biological Mass Spectrometry Shared Resource (A.D., K.C.H.), Department of Anesthesiology (N.J.S.), Advanced Light Microscopy Core Facility (R.M.), Department of Dermatology (H.L., H.L., Q.Z.), and Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition (K.C.E.K.), University of Colorado, Denver; Department of Mitochondrial Physiology, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic (L.P.-H., P.J.); Department of Lung Development and Remodeling, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany (D.I., S.P.); Center for Genetic Improvement of Livestock, Department of Animal Bioscience, University of Guelph, Guelph, ON, Canada (A.C.); Department of Animal Science, University of California-Davis, Davis (J.F.M.); and Department of Animal Science, Colorado State University, Fort Collins (M.G.T.)
Stenmark, Kurt R
Autor Stenmark, Kurt R From Cardiovascular Pulmonary Research Laboratories, Department of Pediatrics and Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO (M.L., S.R., H.Z., A.F., B.A.M., M.F., S.K., M.A.F., K.R.S.); Department of Biochemistry and Molecular Genetics and Biological Mass Spectrometry Shared Resource (A.D., K.C.H.), Department of Anesthesiology (N.J.S.), Advanced Light Microscopy Core Facility (R.M.), Department of Dermatology (H.L., H.L., Q.Z.), and Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition (K.C.E.K.), University of Colorado, Denver; Department of Mitochondrial Physiology, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic (L.P.-H., P.J.); Department of Lung Development and Remodeling, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany (D.I., S.P.); Center for Genetic Improvement of Livestock, Department of Animal Bioscience, University of Guelph, Guelph, ON, Canada (A.C.); Department of Animal Science, University of California-Davis, Davis (J.F.M.); and Department of Animal Science, Colorado State University, Fort Collins (M.G.T.). kurt.stenmark@ucdenver.edu

Circulation. 2016 Oct 11 ; 134 (15) : 1105-1121. [epub] 20160825

ISSN 1524-4539 | 0009-7322
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Jazyk angličtina Země Spojené státy americké Médium print-electronic

Typ dokumentu časopisecké články

Perzistentní odkaz https://www.medvik.cz/link/pmid27562971

Grantová podpora
T32 HL007171 NHLBI NIH HHS - United States
P30 CA046934 NCI NIH HHS - United States
P01 HL014985 NHLBI NIH HHS - United States
R01 HL114887 NHLBI NIH HHS - United States
P50 HL084923 NHLBI NIH HHS - United States

Online Plný text

PubMed 27562971
PubMed Central PMC5069179
DOI 10.1161/circulationaha.116.023171
PII: CIRCULATIONAHA.116.023171
Knihovny.cz E-zdroje

Klíčová slova
cell proliferation, fibroblasts, glycolysis, hypertension, pulmonary, metabolism,
MeSH
adventicie metabolismus patologie MeSH
alkoholoxidoreduktasy genetika metabolismus MeSH
DNA vazebné proteiny genetika metabolismus MeSH
familiární plicní arteriální hypertenze genetika metabolismus patologie MeSH
fenotyp MeSH
fibroblasty metabolismus patologie MeSH
kultivované buňky MeSH
lidé MeSH
myši MeSH
plicní hypertenze metabolismus patologie MeSH
zvířata MeSH
Check Tag
lidé MeSH
myši MeSH
zvířata MeSH
Publikační typ
časopisecké články MeSH
Názvy látek
alkoholoxidoreduktasy MeSH
C-terminal binding protein MeSH Prohlížeč
DNA vazebné proteiny MeSH

BACKGROUND: Changes in metabolism have been suggested to contribute to the aberrant phenotype of vascular wall cells, including fibroblasts, in pulmonary hypertension (PH). Here, we test the hypothesis that metabolic reprogramming to aerobic glycolysis is a critical adaptation of fibroblasts in the hypertensive vessel wall that drives proliferative and proinflammatory activation through a mechanism involving increased activity of the NADH-sensitive transcriptional corepressor C-terminal binding protein 1 (CtBP1). METHODS: RNA sequencing, quantitative polymerase chain reaction,13C-nuclear magnetic resonance, fluorescence-lifetime imaging, mass spectrometry-based metabolomics, and tracing experiments with U-13C-glucose were used to assess glycolytic reprogramming and to measure the NADH/NAD+ ratio in bovine and human adventitial fibroblasts and mouse lung tissues. Immunohistochemistry was used to assess CtBP1 expression in the whole-lung tissues. CtBP1 siRNA and the pharmacological inhibitor 4-methylthio-2-oxobutyric acid (MTOB) were used to abrogate CtBP1 activity in cells and hypoxic mice. RESULTS: We found that adventitial fibroblasts from calves with severe hypoxia-induced PH and humans with idiopathic pulmonary arterial hypertension (PH-Fibs) displayed aerobic glycolysis when cultured under normoxia, accompanied by increased free NADH and NADH/NAD+ ratios. Expression of the NADH sensor CtBP1 was increased in vivo and in vitro in fibroblasts within the pulmonary adventitia of humans with idiopathic pulmonary arterial hypertension and animals with PH and cultured PH-Fibs, respectively. Decreasing NADH pharmacologically with MTOB or genetically blocking CtBP1 with siRNA upregulated the cyclin-dependent genes (p15 and p21) and proapoptotic regulators (NOXA and PERP), attenuated proliferation, corrected the glycolytic reprogramming phenotype of PH-Fibs, and augmented transcription of the anti-inflammatory gene HMOX1. Chromatin immunoprecipitation analysis demonstrated that CtBP1 directly binds the HMOX1 promoter. Treatment of hypoxic mice with MTOB decreased glycolysis and expression of inflammatory genes, attenuated proliferation, and suppressed macrophage numbers and remodeling in the distal pulmonary vasculature. CONCLUSIONS: CtBP1 is a critical factor linking changes in cell metabolism to cell phenotype in hypoxic and other forms of PH and a therapeutic target.

From Cardiovascular Pulmonary Research Laboratories Department of Pediatrics and Medicine University of Colorado Anschutz Medical Campus Aurora CO

Erratum v

Circulation. 2019 Jan 8;139(2):e1. doi: 10.1161/CIR.0000000000000647. PubMed Moldvan, Radu [corrected to Moldovan, Radu]

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