TY - JOUR
T1 - Vascular endothelial growth factor receptor inhibition enhances chronic obstructive pulmonary disease picture in mice exposed to waterpipe smoke
AU - Alzoubi, A.
AU - Ghazwi, R.
AU - Alzoubi, K.
AU - Alqudah, M.
AU - Kheirallah, K.
AU - Khabour, O.
AU - Allouh, M.
N1 - Publisher Copyright:
Copyright © 2018 Via Medica.
PY - 2018/9/5
Y1 - 2018/9/5
N2 - Background: Chronic obstructive pulmonary disease (COPD) is marked by destruction of alveolar architecture. Preclinical modelling for COPD is challenging. Chronic cigarette smoke exposure, the reference animal model of COPD, is time-inefficient, while exposure to waterpipe smoke (WPS), a surging smoking modality, was not fully tested for its histopathological pulmonary consequences. Since alveolar damage and pulmonary vascular endothelial dysfunction are integral to COPD pathology, lung histopathological effects of WPS were temporally evaluated, alone or in combination with vascular endothelial growth factor receptor (VEGFR) inhibition in mice. Materials and methods: Mice were exposed to WPS, 3 hours/day, 5 days/week, for 1, 2, 3, or 4 months. Another group of mice was exposed to WPS for 1 month, while being subjected to injections with the VEGFR blocker Sugen5416 (SU, 20 mg/kg) 3 times weekly. Control mice were exposed to fresh air in a matching inhalation chamber. Histopathological assessment of COPD was performed. Alveolar destructive index (DI) was counted as the percentage of abnormally enlarged alveoli with damaged septa per all alveoli counted. Mean linear intercept (MLI) was calculated as a measure of airspace enlargement. Results: Exposure to WPS resulted in significant increases in alveolar DI and MLI only after 4 months. Lung inflammatory score was minimal across all time-points. Importantly, combination of WPS and SU resulted in significantly increased DI, MLI, and inflammatory scores as early as 1 month post exposure. Conclusions: Combined exposure to WPS and SU results in COPD picture, highlighting the role of pulmonary vascular endothelial dysfunction in the disease.
AB - Background: Chronic obstructive pulmonary disease (COPD) is marked by destruction of alveolar architecture. Preclinical modelling for COPD is challenging. Chronic cigarette smoke exposure, the reference animal model of COPD, is time-inefficient, while exposure to waterpipe smoke (WPS), a surging smoking modality, was not fully tested for its histopathological pulmonary consequences. Since alveolar damage and pulmonary vascular endothelial dysfunction are integral to COPD pathology, lung histopathological effects of WPS were temporally evaluated, alone or in combination with vascular endothelial growth factor receptor (VEGFR) inhibition in mice. Materials and methods: Mice were exposed to WPS, 3 hours/day, 5 days/week, for 1, 2, 3, or 4 months. Another group of mice was exposed to WPS for 1 month, while being subjected to injections with the VEGFR blocker Sugen5416 (SU, 20 mg/kg) 3 times weekly. Control mice were exposed to fresh air in a matching inhalation chamber. Histopathological assessment of COPD was performed. Alveolar destructive index (DI) was counted as the percentage of abnormally enlarged alveoli with damaged septa per all alveoli counted. Mean linear intercept (MLI) was calculated as a measure of airspace enlargement. Results: Exposure to WPS resulted in significant increases in alveolar DI and MLI only after 4 months. Lung inflammatory score was minimal across all time-points. Importantly, combination of WPS and SU resulted in significantly increased DI, MLI, and inflammatory scores as early as 1 month post exposure. Conclusions: Combined exposure to WPS and SU results in COPD picture, highlighting the role of pulmonary vascular endothelial dysfunction in the disease.
KW - Chronic obstructive pulmonary disease
KW - Sugen5416
KW - Vascular endothelial growth factor receptor
KW - Waterpipe smoke
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U2 - 10.5603/FM.a2017.0120
DO - 10.5603/FM.a2017.0120
M3 - Article
C2 - 29297179
AN - SCOPUS:85053280465
SN - 0015-5659
VL - 77
SP - 447
EP - 455
JO - Folia Morphologica
JF - Folia Morphologica
IS - 3
ER -