Direct effect of cigarette smoke on human pulmonary artery tension

Ortiz, J.L.; Milara, Javier; Juan, Gustavo Alberto San; Montesinos, José Luis González; Mata, Manuel; Ramón, M.; Morcillo, Esteban J.; Cortijo, Julio

doi:10.1016/j.pupt.2009.11.001

Cited by 21 publications

(17 citation statements)

References 33 publications

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“…Several growth factors and pro-inflammatory mediators, such as transforming growth factor (TGF)-b1, interleukin-13 and connective tissue growth factor, have been described as inducers of myofibroblast transition [18]; however, no data were available on cigarette smoke, the main risk factor for COPD. In this work, we prepared CSE as we and others have described previously [13,14], which approximately corresponds to exposures associated with smoking slightly fewer than 0.5 packs per day to slightly fewer than 2 packs per day of cigarettes for CSE 2.5% and 10%, respectively. Currently, several in vitro studies have been focused on effect of CSE on lung fibroblasts; however, no data are available on effect of CSE on bronchial fibroblast to myofibroblast transition.…”

Section: Discussionmentioning

confidence: 99%

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Aclidinium inhibits cigarette smoke-induced lung fibroblast-to-myofibroblast transition

Milara

Serrano

Peiró³

et al. 2012

Eur Respir J

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Cigarette smoking contributes to lung remodelling in chronic obstructive pulmonary disease (COPD). As part of this remodelling, peribronchiolar fibrosis is observed in the small airways of COPD patients and contributes to airway obstruction. Fibroblast-to-myofibroblast transition is a key step in peribronchiolar fibrosis formation.This in vitro study examined the effect of cigarette smoke on bronchial fibroblast-tomyofibroblast transition, and whether aclidinium bromide inhibits this process. Human bronchial fibroblasts were incubated with aclidinium bromide (10 -9 -10 -7 M) and exposed to cigarette smoke extract. Collagen type I and a-smooth muscle actin (a-SMA) expression were measured by realtime PCR and Western blotting, as myofibroblast markers. Intracellular reactive oxygen species, cyclic AMP (cAMP), extracellular signal-regulated kinase (ERK)1/2 and choline acetyltransferase were measured as intracellular signalling mediators. Cigarette smoke-induced collagen type I and a-SMA was mediated by the production of reactive oxygen species, the depletion of intracellular cAMP and the increase of ERK1/2 phosphorylation and choline acetyltransferase. These effects could be reversed by treatment with the anticholinergic aclidinium bromide, by silencing the mRNA of muscarinic receptors M1, M2 or M3, or by the depletion of extracellular acetylcholine by treatment with acetylcholinesterase.A non-neuronal cholinergic system is implicated in cigarette smoke-induced bronchial fibroblast-to-myofibroblast transition, which is inhibited by aclidinium bromide.

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Section: Discussionmentioning

confidence: 99%

“…Cigarette smoke extract (CSE) solutions were prepared as previously described [13]. Briefly, the smoke of a research cigarette (2R4F; Tobacco Health Research, University of Kentucky, Lexington, KY, USA) was bubbled into a flask containing 25 mL pre-warmed (37uC) Dulbecco's Modified Eagle's Medium.…”

Section: Preparation Of Cigarette Smoke Extract and Incubationsmentioning

confidence: 99%

Aclidinium inhibits cigarette smoke-induced lung fibroblast-to-myofibroblast transition

Milara

Serrano

Peiró³

et al. 2012

Eur Respir J

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“…Cigarette smoke extract (CSE) was prepared as previously reported [19]. Briefly, CSE was prepared by bubbling the smoke from two cigarettes into 20 ml of serum-free DMEM, which was then filtered with a 0.2 µm filter to sterilize the mixture.…”

Section: Methodsmentioning

confidence: 99%

Effect of Liuweibuqi Capsules in Pulmonary Alveolar Epithelial Cells and COPD Through JAK/STAT Pathway

Wang¹,

Ding²,

Tang³

et al. 2017

Cell Physiol Biochem

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Background/Aims: To evaluate the effect of Liuweibuqi capsules on chronic obstructive pulmonary disease (COPD) through the JAK/STAT pathway. Methods: Lung function was measured with a spirometer. Changes in lung histology were observed using H&E staining. Cigarette smoke extract combined with lipopolysaccharide (CSE+LPS) was used to establish the cellular COPD model. Cytokine levels were determined using ELISA, and changes in the JAK/STAT pathway were evaluated using western blotting. The CCK8 method and flow cytometry were used to measure cell viability and apoptosis, respectively. Results: Liuweibuqi capsules reduced the damage in the lung tissues and the loss of lung function in the COPD rats. Additionally, the levels of interleukin (IL)-1β, interferon γ (IFNγ), IL-6, tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-β1 were higher, whereas IL-10 was lower in the model control (MC) and CSE+LPS groups than in the normal group. The phosphorylation levels of JAK1, JAK2, STAT1, STAT3 and STAT5 were higher and the levels of SOCS1 and SOCS3 were lower in the MC group and CSE+LPS group compared with the normal group. After Liuweibuqi capsule treatment, the expression of inflammatory cytokines and elements of the JAK/STAT pathway were lower. In addition, over-expression of STAT3 blocked the effects of the Liuweibuqi capsules on the release of inflammatory cytokines, cell viability and apoptosis. Conclusion: Our findings suggested that Liuweibuqi capsule might effectively ameliorate the progression of COPD via the JAK/STAT pathway.

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“…HPASMCs were isolated from surgical specimens of human pulmonary arteries as previously outlined [12]. Briefly, segments of pulmonary artery (internal diameter 2-3 mm) were digested with 1% collagenase (Gibco, Paisley, UK) in RPMI-1640 culture medium for 30 min at 37uC.…”

Section: Isolation and Culture Of Hpasmcsmentioning

confidence: 99%

“…Briefly, segments of pulmonary artery (internal diameter 2-3 mm) were digested with 1% collagenase (Gibco, Paisley, UK) in RPMI-1640 culture medium for 30 min at 37uC. HPASMCs were isolated from human pulmonary artery endothelial cells (HPAECs) by means of CD31-coated Dynabeads (Dynal Biotech, Darmstadt, Germany) as previously outlined [12] and cultured in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% fetal calf serum, 1% fungizone and 2% streptomycin/penicillin. All HPASMCs studied were used from passage 1 to 4.…”

Section: Isolation and Culture Of Hpasmcsmentioning

confidence: 99%

Bosentan inhibits cigarette smoke-induced endothelin receptor expression in pulmonary arteries

Milara

Gabarda²,

Juan³

et al. 2011

Eur Respir J

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The endothelin (ET) system contributes to lung vascular tension and remodelling in smokers and chronic obstructive pulmonary disease (COPD) patients.This study examined the effect of cigarette smoke (CS) on ET receptor A (ETA) and B (ETB) expression in human pulmonary artery smooth muscle cells (HPASMCs) and human small intrapulmonary arteries, as well as their functional consequences.CS extract (CSE) increased ETA and ETB expression in HPASMCs and small intrapulmonary arteries, which was attenuated by bosentan, the ETA antagonist BQ123 and the ETB antagonist BQ788, and by blocking ET-1 with a monoclonal antibody against ET-1, suggesting a feed-forward mechanism mediated by ET-1 release. ET receptor (ETR) antagonism attenuated the CSE-induced HPASMC proliferation. Furthermore, CSE exposure increased the acute ET-1-induced small intrapulmonary artery contraction, which was attenuated by bosentan, BQ123 and BQ788. Pulmonary arteries from smokers and COPD patients showed a higher expression of ETA and ETB than those of nonsmoker patients.These results show a novel mechanism by which ETR blockade attenuates CS-induced ETR overexpression and, subsequently, small intrapulmonary artery tension. These data may be of potential value to explain therapeutic effects of bosentan in some forms of disproportionate pulmonary hypertension in COPD patients.KEYWORDS: Bosentan, cigarette smoke, endothelin receptor, human pulmonary artery smooth muscle cells, precision-cut lung slice P ulmonary hypertension (PH) is a relatively common form of cigarette smoke (CS)-induced lung disease. PH develops in ,6% of subjects with chronic obstructive pulmonary disease (COPD) but is present in ,40% of patients with a forced expiratory volume in 1 s of ,1 L [1, 2]. The pathogenesis of PH in COPD is unclear. Current studies suggest that PH is caused by the direct effects of CS on the intrapulmonary vessels by the secretion of a number of vasoconstrictive/proliferative peptides, such as endothelin (ET) or vascular endothelial growth factor, which subsequently contribute to vascular remodelling and the development of PH [3]. The circulating levels of ET-1 are elevated after exposure to CS in humans [4] and it has been shown that ET-1 correlates with pulmonary systolic pressure in COPD patients with PH [5], suggesting that ET-1 is involved in CS-induced vascular remodelling. ET-1 activates two receptors, ETA and ETB, which are located in pulmonary artery smooth muscle cells (PASMCs), whilst exclusively ETB are present in endothelial cells. Both ETA and ETB mediate proliferation and contractility in PASMCs from small pulmonary arteries, while endothelial ETB mediates vasodilation in normal pulmonary arteries. ETB upregulation has been observed in human blood vessels from patients with ischaemic heart disease [6], hypertension [7] and severe PH [8]. More recently, it has been shown that CS extract (CSE) induces ETA and ETB overexpression in resistant cerebral arteries from rats by a mechanism implicating the activation of the intracellular m...

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Direct effect of cigarette smoke on human pulmonary artery tension

Cited by 21 publications

References 33 publications

Aclidinium inhibits cigarette smoke-induced lung fibroblast-to-myofibroblast transition

Aclidinium inhibits cigarette smoke-induced lung fibroblast-to-myofibroblast transition

Effect of Liuweibuqi Capsules in Pulmonary Alveolar Epithelial Cells and COPD Through JAK/STAT Pathway

Bosentan inhibits cigarette smoke-induced endothelin receptor expression in pulmonary arteries

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