ArticleEMBO molecular medicine2021
Histamine signaling and metabolism identify potential biomarkers and therapies for lymphangioleiomyomatosis.
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Article in EMBO molecular medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11citing papers in PubMed
1.7field-weighted citation impact, top 16% of its field
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Who cites it
11 citing papers in PubMed, 20 citations in OpenAlex.
- Current insight into the molecular mechanisms of lymphangioleiomyomatosis.American journal of respiratory cell and molecular biology · 2026Review
- Exploring glucocorticoid receptor signalling in lymphangioleiomyomatosis.ERJ open research · 2026Article
- Investigating the potential role of propionylcarnitine in milk pentadecanoic acid synthesis in Chinese holstein dairy cows using multi-omics analysis.BMC genomics · 2026Article
- Dual-signal histamine aptasensor design based on SERS and electrochemical effects of gold nanomaterials.Mikrochimica acta · 2026Article
- Subtype-specific dysregulation of biogenic amine-related genes and miRNAs in breast cancer: identification of DRD2, HRH2, and HRH4 as potential therapeutic targets in TNBC and HER2+ subtypes.Breast cancer research and treatment · 2025Article
- Novel treatment strategies for lymphangioleiomyomatosis: a narrative review.European respiratory review : an official journal of the European Respiratory Society · 2025Review
- LncRNA MIR100HG affects the proliferation and metastasis of lung cancer cells through mediating the microRNA-5590-3p/DCBLD2 axis.Immunity, inflammation and disease · 2024Article
- The role of moesin in diagnosing and assessing severity of lymphangioleiomyomatosis.Respiratory research · 2024Article
- Lymphangioleiomyomatosis: a metastatic lung disease.American journal of physiology. Cell physiology · 2023Review
- Histamine signaling and metabolism identify potential biomarkers and therapies for lymphangioleiomyomatosis.EMBO molecular medicine · 2021Article
- [Highlights 57th SEPAR Congress].Open respiratory archivesReview
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Authors and funding
57 authors at 20 institutions in 6 countries.
Carmen HerranzProCURE, Catalan Institute of Oncology, Oncobell, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Spain.ORCID 0000-0002-2866-0321
Francesca MateoProCURE, Catalan Institute of Oncology, Oncobell, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Spain.
Alexandra BaigesProCURE, Catalan Institute of Oncology, Oncobell, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Spain.
Gorka Ruiz de GaribayProCURE, Catalan Institute of Oncology, Oncobell, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Spain.ORCID 0000-0001-9936-8419
Alexandra JunzaDepartment of Electronic Engineering, Institute of Health Research Pere Virgili (IIPSV), University Rovira i Virgili, Tarragona, Spain.
Simon R JohnsonNational Centre for Lymphangioleiomyomatosis, Nottingham University Hospitals NHS Trust, Nottinghamshire, Division of Respiratory Medicine, University of Nottingham, Nottingham, UK.ORCID 0000-0002-9837-2763
Suzanne MillerNational Centre for Lymphangioleiomyomatosis, Nottingham University Hospitals NHS Trust, Nottinghamshire, Division of Respiratory Medicine, University of Nottingham, Nottingham, UK.
Nadia GarcíaProCURE, Catalan Institute of Oncology, Oncobell, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Spain.
Jordi CapelladesDepartment of Electronic Engineering, Institute of Health Research Pere Virgili (IIPSV), University Rovira i Virgili, Tarragona, Spain.
Antonio GómezCentre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain.ORCID 0000-0001-5308-981X
August VidalDepartment of Pathology, University Hospital of Bellvitge, Oncobell, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.ORCID 0000-0001-5727-2099
Luis PalomeroProCURE, Catalan Institute of Oncology, Oncobell, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Spain.
Roderic EspínProCURE, Catalan Institute of Oncology, Oncobell, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Spain.
Ana I ExtremeraProCURE, Catalan Institute of Oncology, Oncobell, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Spain.
Eline BlommaertProCURE, Catalan Institute of Oncology, Oncobell, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Spain.
Eva Revilla-LópezLung Transplant Unit, Pneumology Service, Lymphangioleiomyomatosis Clinic, Vall d'Hebron University Hospital, Barcelona, Spain.
Berta SaezLung Transplant Unit, Pneumology Service, Lymphangioleiomyomatosis Clinic, Vall d'Hebron University Hospital, Barcelona, Spain.
Susana Gómez-OllésLung Transplant Unit, Pneumology Service, Lymphangioleiomyomatosis Clinic, Vall d'Hebron University Hospital, Barcelona, Spain.
Julio AncocheaPneumology Service, La Princesa Research Institute, University Hospital La Princesa, Madrid, Spain.
Claudia ValenzuelaPneumology Service, La Princesa Research Institute, University Hospital La Princesa, Madrid, Spain.
Tamara AlonsoPneumology Service, La Princesa Research Institute, University Hospital La Princesa, Madrid, Spain.
Piedad UssettiPneumology Service, University Hospital Clínica Puerta del Hierro, Majadahonda, Madrid, Spain.
Rosalía LaportaPneumology Service, University Hospital Clínica Puerta del Hierro, Majadahonda, Madrid, Spain.
Antoni XaubetPneumology Service, Hospital Clínic de Barcelona, Barcelona, Spain.
José A Rodríguez-PortalMedical-Surgical Unit of Respiratory Diseases, Institute of Biomedicine of Seville (IBiS), University Hospital Virgen del Rocío, Seville, Spain.
Ana Montes-WorboysBiomedical Research Network Centre in Respiratory Diseases (CIBERES), Instituto de Salud Carlos III, Madrid, Spain.
Carlos MachahuaBiomedical Research Network Centre in Respiratory Diseases (CIBERES), Instituto de Salud Carlos III, Madrid, Spain.ORCID 0000-0003-4964-7393
Jaume BordasBiomedical Research Network Centre in Respiratory Diseases (CIBERES), Instituto de Salud Carlos III, Madrid, Spain.ORCID 0000-0003-4027-8907
Javier A MenendezProCURE, Catalan Institute of Oncology, Oncobell, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Spain.
Josep M CruzadoExperimental Nephrology, Department of Clinical Sciences, University of Barcelona, Barcelona, Spain.
Roser GuiterasExperimental Nephrology, Department of Clinical Sciences, University of Barcelona, Barcelona, Spain.
Christophe BontouxDepartment of Pathology, University Hospital Pitié-Salpêtrière, Faculty of Medicine, University of Sorbonne, Paris, France.
Concettina La MottaDepartment of Pharmacy, University of Pisa, Pisa, Italy.ORCID 0000-0002-0194-5431
Aleix Noguera-CastellsBiomedical Research Institute "August Pi i Sunyer" (IDIBAPS), Department of Medicine, University of Barcelona, Barcelona, Spain.
Mario MancinoBiomedical Research Institute "August Pi i Sunyer" (IDIBAPS), Department of Medicine, University of Barcelona, Barcelona, Spain.
Enrique LastraGenetic Counseling Unit, Department of Medical Oncology, University Hospital of Burgos, Burgos, Spain.ORCID 0000-0001-8813-9733
Raúl Rigo-BonninClinical Laboratory, University Hospital of Bellvitge, IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.ORCID 0000-0001-5511-074X
Jose C PeralesDepartment of Physiological Science II, University of Barcelona, Barcelona, Spain.
Francesc ViñalsProCURE, Catalan Institute of Oncology, Oncobell, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Spain.ORCID 0000-0002-9918-6751
Alvaro LahigueraProCURE, Catalan Institute of Oncology, Oncobell, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Spain.
Xiaohu ZhangNational Center for Advancing Translational Sciences (NCATS), National Institute of Health (NIH), Bethesda, MD, USA.
Daniel CuadrasStatistics Department, Foundation Sant Joan de Déu, Esplugues, Spain.ORCID 0000-0001-8780-1764
Coline H M van MoorselInterstitial Lung Disease (ILD) Center of Excellence, St. Antonius Hospital, Nieuwegein, The Netherlands.
Joanne J van der VisInterstitial Lung Disease (ILD) Center of Excellence, St. Antonius Hospital, Nieuwegein, The Netherlands.
Marian J R QuanjelInterstitial Lung Disease (ILD) Center of Excellence, St. Antonius Hospital, Nieuwegein, The Netherlands.
Harilaos FilippakisPulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-9013-6344
Razq HakemPrincess Margaret Cancer Centre, University Health Network, Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
Chiara GorriniPrincess Margaret Hospital, The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network, Toronto, ON, Canada.
Marc FerrerNational Center for Advancing Translational Sciences (NCATS), National Institute of Health (NIH), Bethesda, MD, USA.
Aslihan Ugun-KlusekCentre for Health, Ageing and Understanding Disease (CHAUD), School of Science and Technology, Nottingham Trent University, Nottingham, UK.ORCID 0000-0002-0199-0275
Ellen BillettCentre for Health, Ageing and Understanding Disease (CHAUD), School of Science and Technology, Nottingham Trent University, Nottingham, UK.
Elżbieta RadzikowskaDepartment of Lung Diseases III, National Tuberculosis and Lung Disease Research Institute, Warsaw, Poland.ORCID 0000-0002-2585-8594
Álvaro CasanovaPneumology Service, University Hospital of Henares, University Francisco de Vitoria, Coslada, Madrid, Spain.
María Molina-MolinaBiomedical Research Network Centre in Respiratory Diseases (CIBERES), Instituto de Salud Carlos III, Madrid, Spain.
Antonio RomanLung Transplant Unit, Pneumology Service, Lymphangioleiomyomatosis Clinic, Vall d'Hebron University Hospital, Barcelona, Spain.ORCID 0000-0002-9417-3484
Oscar YanesDepartment of Electronic Engineering, Institute of Health Research Pere Virgili (IIPSV), University Rovira i Virgili, Tarragona, Spain.
Miquel A PujanaProCURE, Catalan Institute of Oncology, Oncobell, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Spain.ORCID 0000-0003-3222-4044
Institut d'Investigació Biomédica de Bellvitge · ESInstituto de Salud Carlos III · ESVall d'Hebron Hospital Universitari · ESBellvitge University Hospital · ESHospital Universitario de La Princesa · ESSt. Antonius Ziekenhuis · NLConsorci Institut D'Investigacions Biomediques August Pi I Sunyer · ESHospital Universitario Puerta de Hierro Majadahonda · ESNational Center for Advancing Translational Sciences · USNottingham Trent University · GBNottingham University Hospitals NHS Trust · GBBrigham and Women's Hospital · USCentre for Genomic Regulation · ESHospital Clínic de Barcelona · ESHospital Universitario del Henares · ESOntario Institute for Cancer Research · CASant Joan de Déu Research Foundation · ESUniversitat de Barcelona · ESUniversity Health Network · CAUniversity of Pisa · IT
Funding
Medical Research Council MR/T002042/1
Abstract
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.
Indexed as
Lung NeoplasmsLymphangioleiomyomatosisBiomarkersHistamineHumansSignal TransductionBiomarkersHistaminebiomarkerhistaminelymphangioleiomyomatosismTORtherapy
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