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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Br+J+Pharmacol
2016 ; 173
(22
): 3161-3175
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English Wikipedia
The inhibitor of semicarbazide-sensitive amine oxidase, PXS-4728A, ameliorates
key features of chronic obstructive pulmonary disease in a mouse model
#MMPMID27495192
Jarnicki AG
; Schilter H
; Liu G
; Wheeldon K
; Essilfie AT
; Foot JS
; Yow TT
; Jarolimek W
; Hansbro PM
Br J Pharmacol
2016[Nov]; 173
(22
): 3161-3175
PMID27495192
show ga
BACKGROUND AND PURPOSE: Chronic obstructive pulmonary disease (COPD) is a major
cause of illness and death, often induced by cigarette smoking (CS). It is
characterized by pulmonary inflammation and fibrosis that impairs lung function.
Existing treatments aim to control symptoms but have low efficacy, and there are
no broadly effective treatments. A new potential target is the ectoenzyme,
semicarbazide-sensitive mono-amine oxidase (SSAO; also known as vascular adhesion
protein-1). SSAO is elevated in smokers' serum and is a pro-inflammatory enzyme
facilitating adhesion and transmigration of leukocytes from the vasculature to
sites of inflammation. EXPERIMENTAL APPROACH: PXS-4728A was developed as a low MW
inhibitor of SSAO. A model of COPD induced by CS in mice reproduces key aspects
of human COPD, including chronic airway inflammation, fibrosis and impaired lung
function. This model was used to assess suppression of SSAO activity and
amelioration of inflammation and other characteristic features of COPD. KEY
RESULTS: Treatment with PXS-4728A completely inhibited lung and systemic SSAO
activity induced by acute and chronic CS-exposure. Daily oral treatment inhibited
airway inflammation (immune cell influx and inflammatory factors) induced by
acute CS-exposure. Therapeutic treatment during chronic CS-exposure, when the key
features of experimental COPD develop and progress, substantially suppressed
inflammatory cell influx and fibrosis in the airways and improved lung function.
CONCLUSIONS AND IMPLICATIONS: Treatment with a low MW inhibitor of SSAO,
PXS-4728A, suppressed airway inflammation and fibrosis and improved lung function
in experimental COPD, demonstrating the therapeutic potential of PXS-4728A for
this debilitating disease.