Cigarette smoke extract induces endothelin-1 via protein kinase C in pulmonary artery endothelial cells

Lee, Sangdo; Lee, Dong-Soon; Chun, Yong-Gam; Shim, Tae-Sun; Lim, Chae‐Man; Koh, Younsuck; Kim, Woo-Sung; Kim, Dong‐Soon; Kim, Won-Dong

doi:10.1152/ajplung.2001.281.2.l403

Cited by 33 publications

(27 citation statements)

References 37 publications

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“…This effect was explained because extracellular levels of ET-1 are cleared via endocytosis of ETB; thus, its blockade impedes extracellular ET-1 clearance, inducing ET-1 upregulation. However, the results observed in this study were obtained in the totally different context of CSE exposure; CS increases ET release in endothelial cells and airway SMCs, as previously mentioned [28,29]. In this study, we observed that the CS-induced ET release in HPASMCs was mediated by a mechanism including reactive oxygen generation, ERK1/2 phosphorylation and RhoA-GTP activation.…”

Section: Discussionsupporting

confidence: 59%

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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Section: Discussionsupporting

confidence: 59%

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

Milara

Gabarda²,

Juan³

et al. 2011

Eur Respir J

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“…22,30 However, in many studies, it is emphasized that substances contained in tobacco smoke have a direct and indirect impact on the increased ET-1 expression, which leads to a high concentration of this peptide in the blood of smokers, regardless of the time of exposure. 13,14,31 Cigarette smoking is a major factor disrupting the normal endothelial function and free radicals produced during this process destroy NO. These 2 factors greatly intensify the synthesis of the ET-1 precursor, preproET.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Smoking on Endothelin-1 in Patients With Chronic Pancreatitis

Śliwińska-Mossoń

Nabzdyk²,

Kokot³

et al. 2015

Applied Immunohistochemistry &Amp; Molecular Morphology

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The aim of this study is to prove the influence of tobacco smoking on the endothelin-1 (ET-1) level in the plasma and on the immunohistochemical localization in the pancreatic tissues. The blood was collected from 50 healthy individuals and 63 patients with chronic pancreatitis (CP). The ET-1 and cotinine concentrations in the plasma were estimated by ELISA. Samples of tissues of the normal pancreas and CP were verified histopathologically, and then ET-1 was localized by immunohistochemical staining using the monoclonal anti-human ET-1 antibody. The intensity of immunohistochemical reaction was calculated with the semiquantitative Digital Imaging Methodology. The study demonstrated a significant concentration of ET-1 in smoking healthy individuals and in patients with CP when compared with the nonsmoking population (P=0.003 and 0.0005, respectively). A significantly stronger immunohistochemical ET-1 reaction was observed in the tissue of smoking patients with CP than in the normal pancreatic tissue and of nonsmoking CP patients (P=0.001, 0.008, and 0.03, respectively). The presented data evidence that tobacco smoking has a direct effect on the endothelium, leading to an increased level of ET-1.

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“…There are increased levels of ceremide in smokers, both with and without emphysema (Petrache et al, 2005). In one study (Marwick et al, 2006), VEGFR2 protein expression levels were similar in the lungs of smokers and nonsmokers, although there was decreased expression of VEGFR2 in the smokers with COPD, while another (Lee et al, 2001) demonstrated decreased VEGF and VEGFR2 protein, but only in severe emphysema.…”

Section: Introductionmentioning

confidence: 97%