RT Journal Article
T1 Histamine signaling and metabolism identify potential biomarkers and therapies for lymphangioleiomyomatosis.
A1 Herranz, Carmen
A1 Mateo, Francesca
A1 Baiges, Alexandra
A1 Ruiz de Garibay, Gorka
A1 Junza, Alexandra
A1 Johnson, Simon R
A1 Miller, Suzanne
A1 García, Nadia
A1 Capellades, Jordi
A1 Gómez, Antonio
A1 Vidal, August
A1 Palomero, Luis
A1 Espín, Roderic
A1 Extremera, Ana I
A1 Blommaert, Eline
A1 Revilla-López, Eva
A1 Saez, Berta
A1 Gómez-Ollés, Susana
A1 Ancochea, Julio
A1 Valenzuela, Claudia
A1 Alonso, Tamara
A1 Ussetti, Piedad
A1 Laporta, Rosalía
A1 Xaubet, Antoni
A1 Rodríguez-Portal, José A
A1 Montes-Worboys, Ana
A1 Machahua, Carlos
A1 Bordas, Jaume
A1 Menendez, Javier A
A1 Cruzado, Josep M
A1 Guiteras, Roser
A1 Bontoux, Christophe
A1 La Motta, Concettina
A1 Noguera-Castells, Aleix
A1 Mancino, Mario
A1 Lastra, Enrique
A1 Rigo-Bonnin, Raúl
A1 Perales, Jose C
A1 Viñals, Francesc
A1 Lahiguera, Alvaro
A1 Zhang, Xiaohu
A1 Cuadras, Daniel
A1 van Moorsel, Coline H M
A1 van der Vis, Joanne J
A1 Quanjel, Marian J R
A1 Filippakis, Harilaos
A1 Hakem, Razq
A1 Gorrini, Chiara
A1 Ferrer, Marc
A1 Ugun-Klusek, Aslihan
A1 Billett, Ellen
A1 Radzikowska, Elżbieta
A1 Casanova, Álvaro
A1 Molina-Molina, María
A1 Roman, Antonio
A1 Yanes, Oscar
A1 Pujana, Miquel A
K1 biomarker
K1 histamine
K1 lymphangioleiomyomatosis
K1 mTOR
K1 therapy
AB 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.
YR 2021
FD 2021-08-11
LK http://hdl.handle.net/10668/19505
UL http://hdl.handle.net/10668/19505
LA en
DS RISalud
RD Apr 5, 2025