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2021-08-11

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cc by (c) Herranz, Carmen et al., 2021
Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/179910

Histamine signaling and metabolism identify potential biomarkers and therapies for lymphangioleiomyomatosis

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https://doi.org/10.15252/emmm.202113929

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.

Subject

Marcadors bioquímics, Histamina, Terapèutica

Subject (English)

Biochemical markers, Histamine, Therapeutics

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Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Patologia i Terapèutica Experimental)

Citation

HERRANZ, Carmen, et al. Histamine signaling and metabolism identify potential biomarkers and therapies for lymphangioleiomyomatosis. EMBO Molecular Medicine. 2021. Vol. 13, num. 9, pags. e13929. [consulted: 11 of August of 2026]. Available at: https://hdl.handle.net/2445/179910

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