Sistema de Salut de Catalunya
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
2022-04-25T14:16:04Z
2022-04-25T14:16:04Z
2021-09-07
Biomarcador; Histamina; Limfangioleiomiomatosi
Biomarcador; Histamina; Linfangioleiomiomatosis
Biomarker; Histamine; Lymphangioleiomyomatosis
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.
Article
Published version
English
Pulmons - Càncer - Tractament; Histamina - Receptors; DISEASES::Neoplasms::Neoplasms by Histologic Type::Lymphatic Vessel Tumors::Lymphangiomyoma::Lymphangioleiomyomatosis; Other subheadings::Other subheadings::Other subheadings::/drug therapy; CHEMICALS AND DRUGS::Organic Chemicals::Amines::Biogenic Amines::Biogenic Monoamines::Histamine; DISEASES::Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms; ENFERMEDADES::neoplasias::neoplasias por tipo histológico::tumores de los vasos linfáticos::linfangiomioma::linfangioleiomiomatosis; Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia; COMPUESTOS QUÍMICOS Y DROGAS::compuestos orgánicos::aminas::aminas biógenas::monoaminas biógenas::histamina; ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias torácicas::neoplasias del tracto respiratorio::neoplasias pulmonares
Wiley
EMBO Molecular Medicine;13(9)
https://doi.org/10.15252/emmm.202113929
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
Articles científics - HVH [3439]
