open access

Vol 77, No 3 (2018)
ORIGINAL ARTICLES
Published online: 2017-12-28
Submitted: 2017-10-22
Accepted: 2017-12-13
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Vascular endothelial growth factor receptor inhibition enhances chronic obstructive pulmonary disease picture in mice exposed to waterpipe smoke

A. Alzoubi, R. Ghazwi, K. Alzoubi, M. Alqudah, K. Kheirallah, O. Khabour, M. Allouh
DOI: 10.5603/FM.a2017.0120
·
Pubmed: 29297179
·
Folia Morphol 2018;77(3):447-455.

open access

Vol 77, No 3 (2018)
ORIGINAL ARTICLES
Published online: 2017-12-28
Submitted: 2017-10-22
Accepted: 2017-12-13

Abstract

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.

Abstract

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.

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Keywords

vascular endothelial growth factor receptor; waterpipe smoke; chronic obstructive pulmonary disease; Sugen5416

About this article
Title

Vascular endothelial growth factor receptor inhibition enhances chronic obstructive pulmonary disease picture in mice exposed to waterpipe smoke

Journal

Folia Morphologica

Issue

Vol 77, No 3 (2018)

Pages

447-455

Published online

2017-12-28

DOI

10.5603/FM.a2017.0120

Pubmed

29297179

Bibliographic record

Folia Morphol 2018;77(3):447-455.

Keywords

vascular endothelial growth factor receptor
waterpipe smoke
chronic obstructive pulmonary disease
Sugen5416

Authors

A. Alzoubi
R. Ghazwi
K. Alzoubi
M. Alqudah
K. Kheirallah
O. Khabour
M. Allouh

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