Histamine signaling and metabolism identify potential biomarkers and therapies for lymphangioleiomyomatosis.
Por:
Herranz C, Mateo F, Baiges A, Ruiz de Garibay G, Junza A, Johnson SR, Miller S, García N, Capellades J, Gómez A, Vidal A, Palomero L, Espín R, Extremera AI, Blommaert E, Revilla-López E, Saez B, Gómez-Ollés S, Ancochea J, Valenzuela C, Alonso T, Ussetti P, Laporta R, Xaubet A, Rodríguez-Portal JA, Montes-Worboys A, Machahua C, Bordas J, Menendez JA, Cruzado JM, Guiteras R, Bontoux C, La Motta C, Noguera-Castells A, Mancino M, Lastra E, Rigo-Bonnin R, Perales JC, Viñals F, Lahiguera A, Zhang X, Cuadras-Palleja D, van Moorsel CHM, van der Vis JJ, Quanjel MJR, Filippakis H, Hakem R, Gorrini C, Ferrer M, Ugun-Klusek A, Billett E, Radzikowska E, Casanova Á, Molina-Molina M, Roman A, Yanes O and Pujana MA
Publicada:
7 sep 2021
Ahead of Print:
11 ago 2021
Categoría:
Molecular medicine
Resumen:
Inhibition of mTOR is the standard of care for lymphangioleiomyomatosis (LAM). However, this therapy has variable tolerability and some patients show progressive decline of lung function despite treatment. LAM diagnosis and monitoring can also be challenging due to the heterogeneity of symptoms and insufficiency of non-invasive tests. Here, we propose monoamine-derived biomarkers that provide preclinical evidence for novel therapeutic approaches. The major histamine-derived metabolite methylimidazoleacetic acid (MIAA) is relatively more abundant in LAM plasma, and MIAA values are independent of VEGF-D. Higher levels of histamine are associated with poorer lung function and greater disease burden. Molecular and cellular analyses, and metabolic profiling confirmed active histamine signaling and metabolism. LAM tumorigenesis is reduced using approved drugs targeting monoamine oxidases A/B (clorgyline and rasagiline) or histamine H1 receptor (loratadine), and loratadine synergizes with rapamycin. Depletion of Maoa or Hrh1 expression, and administration of an L-histidine analog, or a low L-histidine diet, also reduce LAM tumorigenesis. These findings extend our knowledge of LAM biology and suggest possible ways of improving disease management.
Filiaciones:
Herranz C:
ProCURE, Catalan Institute of Oncology, Oncobell, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Spain
Mateo F:
ProCURE, Catalan Institute of Oncology, Oncobell, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Spain
Baiges A:
ProCURE, Catalan Institute of Oncology, Oncobell, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Spain
Ruiz de Garibay G:
ProCURE, Catalan Institute of Oncology, Oncobell, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Spain
Junza A:
Department of Electronic Engineering, Institute of Health Research Pere Virgili (IIPSV), University Rovira i Virgili, Tarragona, Spain
Biomedical Research Network Centre in Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain
Johnson SR:
National Centre for Lymphangioleiomyomatosis, Nottingham University Hospitals NHS Trust, Nottinghamshire, Division of Respiratory Medicine, University of Nottingham, Nottingham, UK
Miller S:
National Centre for Lymphangioleiomyomatosis, Nottingham University Hospitals NHS Trust, Nottinghamshire, Division of Respiratory Medicine, University of Nottingham, Nottingham, UK
García N:
ProCURE, Catalan Institute of Oncology, Oncobell, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Spain
Capellades J:
Department of Electronic Engineering, Institute of Health Research Pere Virgili (IIPSV), University Rovira i Virgili, Tarragona, Spain
Biomedical Research Network Centre in Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain
Gómez A:
Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain
Vidal A:
Department of Pathology, University Hospital of Bellvitge, Oncobell, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain
CIBER on Cancer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain
Palomero L:
ProCURE, Catalan Institute of Oncology, Oncobell, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Spain
Espín R:
ProCURE, Catalan Institute of Oncology, Oncobell, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Spain
Extremera AI:
ProCURE, Catalan Institute of Oncology, Oncobell, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Spain
Blommaert E:
ProCURE, Catalan Institute of Oncology, Oncobell, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Spain
Revilla-López E:
Lung Transplant Unit, Pneumology Service, Lymphangioleiomyomatosis Clinic, Vall d'Hebron University Hospital, Barcelona, Spain
Saez B:
Lung Transplant Unit, Pneumology Service, Lymphangioleiomyomatosis Clinic, Vall d'Hebron University Hospital, Barcelona, Spain
Gómez-Ollés S:
Lung Transplant Unit, Pneumology Service, Lymphangioleiomyomatosis Clinic, Vall d'Hebron University Hospital, Barcelona, Spain
Ancochea J:
Pneumology Service, La Princesa Research Institute, University Hospital La Princesa, Madrid, Spain
Valenzuela C:
Pneumology Service, La Princesa Research Institute, University Hospital La Princesa, Madrid, Spain
Alonso T:
Pneumology Service, La Princesa Research Institute, University Hospital La Princesa, Madrid, Spain
Ussetti P:
Pneumology Service, University Hospital Clínica Puerta del Hierro, Majadahonda, Madrid, Spain
Laporta R:
Pneumology Service, University Hospital Clínica Puerta del Hierro, Majadahonda, Madrid, Spain
Xaubet A:
Pneumology Service, Hospital Clínic de Barcelona, Barcelona, Spain
Rodríguez-Portal JA:
Medical-Surgical Unit of Respiratory Diseases, Institute of Biomedicine of Seville (IBiS), University Hospital Virgen del Rocío, Seville, Spain
Biomedical Research Network Centre in Respiratory Diseases (CIBERES), Instituto de Salud Carlos III, Madrid, Spain
Montes-Worboys A:
Biomedical Research Network Centre in Respiratory Diseases (CIBERES), Instituto de Salud Carlos III, Madrid, Spain
Interstitial Lung Disease Unit, Department of Respiratory Medicine, University Hospital of Bellvitge, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain
Machahua C:
Biomedical Research Network Centre in Respiratory Diseases (CIBERES), Instituto de Salud Carlos III, Madrid, Spain
Interstitial Lung Disease Unit, Department of Respiratory Medicine, University Hospital of Bellvitge, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain
Bordas J:
Biomedical Research Network Centre in Respiratory Diseases (CIBERES), Instituto de Salud Carlos III, Madrid, Spain
Interstitial Lung Disease Unit, Department of Respiratory Medicine, University Hospital of Bellvitge, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain
Menendez JA:
ProCURE, Catalan Institute of Oncology, Oncobell, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Spain
Cruzado JM:
Experimental Nephrology, Department of Clinical Sciences, University of Barcelona, Barcelona, Spain
Department of Nephrology, University Hospital of Bellvitge, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain
Guiteras R:
Experimental Nephrology, Department of Clinical Sciences, University of Barcelona, Barcelona, Spain
Department of Nephrology, University Hospital of Bellvitge, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain
Bontoux C:
Department of Pathology, University Hospital Pitié-Salpêtrière, Faculty of Medicine, University of Sorbonne, Paris, France
La Motta C:
Department of Pharmacy, University of Pisa, Pisa, Italy
Noguera-Castells A:
Biomedical Research Institute "August Pi i Sunyer" (IDIBAPS), Department of Medicine, University of Barcelona, Barcelona, Spain
Mancino M:
Biomedical Research Institute "August Pi i Sunyer" (IDIBAPS), Department of Medicine, University of Barcelona, Barcelona, Spain
Lastra E:
Genetic Counseling Unit, Department of Medical Oncology, University Hospital of Burgos, Burgos, Spain
Rigo-Bonnin R:
Clinical Laboratory, University Hospital of Bellvitge, IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain
Perales JC:
Department of Physiological Science II, University of Barcelona, Barcelona, Spain
Viñals F:
ProCURE, Catalan Institute of Oncology, Oncobell, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Spain
Department of Physiological Science II, University of Barcelona, Barcelona, Spain
Lahiguera A:
ProCURE, Catalan Institute of Oncology, Oncobell, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Spain
Zhang X:
National Center for Advancing Translational Sciences (NCATS), National Institute of Health (NIH), Bethesda, MD, USA
Cuadras-Palleja D:
Statistics Department, Foundation Sant Joan de Déu, Esplugues, Spain
van Moorsel CHM:
Interstitial Lung Disease (ILD) Center of Excellence, St. Antonius Hospital, Nieuwegein, The Netherlands
van der Vis JJ:
Interstitial Lung Disease (ILD) Center of Excellence, St. Antonius Hospital, Nieuwegein, The Netherlands
Quanjel MJR:
Interstitial Lung Disease (ILD) Center of Excellence, St. Antonius Hospital, Nieuwegein, The Netherlands
Filippakis H:
Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
Hakem R:
Princess Margaret Cancer Centre, University Health Network, Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada
Gorrini C:
Princess Margaret Hospital, The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network, Toronto, ON, Canada
Ferrer M:
National Center for Advancing Translational Sciences (NCATS), National Institute of Health (NIH), Bethesda, MD, USA
Ugun-Klusek A:
Centre for Health, Ageing and Understanding Disease (CHAUD), School of Science and Technology, Nottingham Trent University, Nottingham, UK
Billett E:
Centre for Health, Ageing and Understanding Disease (CHAUD), School of Science and Technology, Nottingham Trent University, Nottingham, UK
Radzikowska E:
Department of Lung Diseases III, National Tuberculosis and Lung Disease Research Institute, Warsaw, Poland
Casanova Á:
Pneumology Service, University Hospital of Henares, University Francisco de Vitoria, Coslada, Madrid, Spain
Molina-Molina M:
Biomedical Research Network Centre in Respiratory Diseases (CIBERES), Instituto de Salud Carlos III, Madrid, Spain
Interstitial Lung Disease Unit, Department of Respiratory Medicine, University Hospital of Bellvitge, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain
Roman A:
Lung Transplant Unit, Pneumology Service, Lymphangioleiomyomatosis Clinic, Vall d'Hebron University Hospital, Barcelona, Spain
Yanes O:
Department of Electronic Engineering, Institute of Health Research Pere Virgili (IIPSV), University Rovira i Virgili, Tarragona, Spain
Biomedical Research Network Centre in Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain
Pujana MA:
ProCURE, Catalan Institute of Oncology, Oncobell, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Spain
Green Published
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