Histamine signaling and metabolism identify potential biomarkers and therapies for lymphangioleiomyomatosis

Autor: Coline H M van Moorsel, Ana Montes-Worboys, Razq Hakem, E. Ellen Billett, Carmen Herranz, Eline Blommaert, Oscar Yanes, Antonio Roman, Julio Ancochea, Álvaro Casanova, Raúl Rigo-Bonnin, Harilaos Filippakis, Berta Saez, August Vidal, Alexandra Baiges, Antoni Xaubet, Suzanne Miller, Antonio Gomez, Roderic Espín, Joanne J van der Vis, José A Rodríguez-Portal, Chiara Gorrini, Jaume Bordas, Marian J R Quanjel, Aleix Noguera-Castells, Luis Palomero, Eva Revilla-López, Josep M. Cruzado, Xiaohu Zhang, Enrique Lastra, Nadia García, Elżbieta Radzikowska, Marc Ferrer, Simon R. Johnson, Christophe Bontoux, Maria Molina-Molina, Alexandra Junza, Javier A. Menendez, Ana I. Extremera, Piedad Ussetti, Rosalía Laporta, Álvaro Lahiguera, Miquel Angel Pujana, Susana Gómez-Ollés, Daniel Cuadras, Mario Mancino, Claudia Valenzuela, Tamara Alonso, Jose C. Perales, Francesca Mateo, Francesc Viñals, Aslihan Ugun-Klusek, Gorka Ruiz de Garibay, Roser Guiteras, Jordi Capellades, Concettina La Motta, Carlos Machahua
Přispěvatelé: Asociación Española de Linfangioleiomiomatosis, Instituto de Salud Carlos III, European Commission, Generalitat de Catalunya, Università di Pisa, Nottingham Trent University, Institut Català de la Salut, [Herranz C, Mateo F, Baiges A, 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] Department of Electronic Engineering, Institute of Health Research Pere Virgili (IIPSV), University Rovira i Virgili, Tarragona, Spain. [Revilla-López E, Saez B, Gómez-Ollés S, Roman A] Unitat de Trasplantament Pulmonar, Servei de Pneumologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus
Rok vydání: 2021
Předmět:
Medicine (General)
Lung Neoplasms
Respiratory System
QH426-470
Loratadine
Pharmacology
Other subheadings::Other subheadings::/drug therapy [Other subheadings]
chemistry.chemical_compound
neoplasias::neoplasias por localización::neoplasias torácicas::neoplasias del tracto respiratorio::neoplasias pulmonares [ENFERMEDADES]
biomarker
Lymphangioleiomyomatosis
neoplasias::neoplasias por tipo histológico::tumores de los vasos linfáticos::linfangiomioma::linfangioleiomiomatosis [ENFERMEDADES]
Cancer
Biochemical markers
histamine
lymphangioleiomy omatosis
Articles
Tolerability
Histamina
Marcadors bioquímics
mTOR
Molecular Medicine
Biomarker (medicine)
Neoplasms::Neoplasms by Histologic Type::Lymphatic Vessel Tumors::Lymphangiomyoma::Lymphangioleiomyomatosis [DISEASES]
therapy
Histamina - Receptors
Histamine
compuestos orgánicos::aminas::aminas biógenas::monoaminas biógenas::histamina [COMPUESTOS QUÍMICOS Y DROGAS]
medicine.drug
Signal Transduction
Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms [DISEASES]
Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores]
Histamine H1 receptor
Therapeutics
Article
R5-920
Genetics
medicine
Humans
PI3K/AKT/mTOR pathway
Rasagiline
Organic Chemicals::Amines::Biogenic Amines::Biogenic Monoamines::Histamine [CHEMICALS AND DRUGS]
business.industry
medicine.disease
Terapèutica
lymphangioleiomyomatosis
Metabolism
chemistry
Therapy
business
Limfoangiomiomatosi
Pulmons - Càncer - Tractament
Biomarkers
Zdroj: Digital.CSIC. Repositorio Institucional del CSIC
instname
EMBO Molecular Medicine
r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
Scientia
DDFV. Repositorio Institucional de la Universidad Francisco de Vitoria
Dipòsit Digital de la UB
Universidad de Barcelona
EMBO Molecular Medicine, Vol 13, Iss 9, Pp n/a-n/a (2021)
ISSN: 8420-0200
1757-4676
Popis: 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.
This research was supported by AELAM, The LAM Foundation (Seed Grant 2019), Instituto de Salud Carlos III grants PI15/00854, PI18/01029, and ICI19/00047 (co-funded by European Regional Development Fund (ERDF), a way to build Europe), Generalitat de Catalunya SGR grants 2014-364 and 2017-449, the CERCA Program, and ZonMW-TopZorg grant 842002003. C.L.M. acknowledges the financial support (PRA-2017-51 project) of the University of Pisa. A.U.K. is supported by Nottingham Trent University’s Independent Fellowship Scheme.
Databáze: OpenAIRE
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