scholarly journals Direct Effects of Cigarette Smoke in Pulmonary Arterial Cells alter Vascular Tone through Arterial Remodeling and Kv7.4 Channel Dysregulation

2019 ◽  
Author(s):  
J Sevilla-Montero ◽  
D Labrousse-Arias ◽  
C Fernández-Pérez ◽  
B Barreira ◽  
G Mondejar-Parreño ◽  
...  
Keyword(s):  
Cigarette Smoke ◽  
Molecular Mechanisms ◽  
Pulmonary Arteries ◽  
Pulmonary Vasculature ◽  
Chronic Obstructive ◽  
Proliferative Potential ◽  
Direct Effects ◽  
Obstructive Pulmonary Disease ◽  
Cell Contractility ◽  
Pulmonary Arterial

AbstractChronic obstructive pulmonary disease (COPD) is a widespread disease, with no curative therapies nowadays. Exposure to cigarette smoking is considered the chief leading cause of COPD. Current drugs therapies improve patient quality of life, however they do not revert the progression of the disease. Therefore, a deeper study of the cellular and molecular mechanisms that underlie this pathology is required to be able to carry out targeted and effective treatments. Although the effects of cigarette smoke in the progressive deterioration of the airway have been extensively studied in COPD patients, its effects on pulmonary vasculature have been unexplored, due to the classic conception that vascular damage is a consequence of alveolar hypoxia and loss of capillary bed. In this paper, we aimed to study the effects of cigarette smoke extract (CSE) in regulating pulmonary arterial cells phenotypic modulation, in particular the effects in fibroblasts (hPAFib) and smooth muscle cells (hPASMC), and in murine pulmonary arteries. Our results demonstrated that CSE exposure had direct effects on hPAFib and hPASMC, promoting a senescent phenotype that in turn contributed, through the secretion of inflammatory molecules, to increase the proliferative potential of non-exposed cells. CSE also increased total ROS levels in hPAFib and hPASMC, and upregulated NADPH oxidase subunits NOX1 and p22phox. Most importantly, CSE affected cell contractility and dysregulated the expression and activity of voltage-gated K+ channel Kv7.4. This contributed to limit vascular responses impairing vasoconstriction and endothelium-dependent and independent relaxation.

ET-1 modulates KCa-channel activity and arterial tension in normoxic and hypoxic human pulmonary vasculature

1998 ◽  
Vol 275 (4) ◽  
pp. L729-L739 ◽  
Author(s):  
Wei Peng ◽  
John R. Michael ◽  
John R. Hoidal ◽  
S. V. Karwande ◽  
Imad S. Farrukh
Keyword(s):  
Pulmonary Hypertension ◽  
Molecular Mechanisms ◽  
Pulmonary Vasculature ◽  
Chronic Obstructive ◽  
Intact Cells ◽  
Obstructive Pulmonary Disease ◽  
Human Organ ◽  
Channel Current ◽  
Intracellular Ca ◽  
Pulmonary Arterial

The molecular mechanisms by which endothelin (ET)-1 induces pulmonary hypertension are poorly understood. We investigated the effects of ET-1 on outward K+ currents of normoxic and chronically hypoxic human pulmonary arterial (PA) smooth muscle cells (HPSMCs). In normoxic HPSMCs, ET-1 has dual effects. In intact cells, 5 nM ET-1 activates the large-conductance and Ca2+-activated K+(KCa)-channel current [ I K(Ca)] by increasing intracellular Ca2+concentration, whereas it directly inhibits I K(Ca) in isolated membrane patches. At a higher concentration (10 nM), ET-1-induced I K(Ca) inhibition predominates. In hypoxic HPSMCs, ET-1 at 5 nM significantly reduces I K(Ca). The ETA-receptor antagonist BQ-123 reverses the ET-1-induced decrease in I K(Ca). Chronic BQ-123 treatment also prevents the hypoxia-induced decrease in I K(Ca). In PA rings obtained from human organ donors, ET-1 causes a concentration-dependent increase in tension. The ET-1-mediated increase in tension is reversed by a KCa-channel agonist. The increase in tension at the highest concentration studied (9 nM) was more pronounced in PA rings obtained from patients with chronic obstructive pulmonary disease. These results imply that an ET-1-induced decrease in I K(Ca)contributes to chronic hypoxia-induced pulmonary hypertension.

Chrysene accelerates the proceeding of chronic obstructive pulmonary disease with the aggravation of inflammation and apoptosis in cigarette smoke exposed mice

2020 ◽  
pp. 096032712097934
Author(s):  
Yuan Gao ◽  
Xinjia Zhou ◽  
Yan Zhou ◽  
Wei Zhang ◽  
Li Zhao
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Cigarette Smoke ◽  
Molecular Mechanisms ◽  
Smooth Muscle Actin ◽  
Lavage Fluid ◽  
Living Environment ◽  
Chronic Obstructive ◽  
High Morbidity ◽  
Obstructive Pulmonary Disease

Chrysene, one of the basic polycyclic aromatic hydrocarbons (PAHs), has been reported to make damages to human health and living environment. Chronic obstructive pulmonary disease (COPD) is a progressive disorder with high morbidity and mortality. To investigate the role of chrysene in the development of COPD, male C57BL/6 mice were exposed to the cigarette smoke (CS) followed with the administration of chrysene. Morphological analyses indicated that chrysene caused earlier and severer pathological changes in CS-exposed mice. Besides, CS-exposed mice with chrysene treatment showed obvious collagen deposition, elevated α-smooth muscle actin (α-SMA) expression and reduced E-cadherin abundance at earlier stage, which suggested the acceleration and aggravation of pulmonary fibrosis. Moreover, quantification of leukocytes and pro-inflammatory cytokines in bronchoalveolar lavage fluid (BALF) and lung tissues implied that chrysene significantly exacerbated the proceeding of inflammation in CS-exposed mice. Furthermore, significantly increased apoptotic rates, augmented expressions of apoptotic related proteins and highly expressed TRPV1 were determined in CS-exposed mice with chrysene treatment, which indicated the association between COPD pathogenesis and TRPV1 channel. In summary, our findings elucidate that chrysene accelerates the development of COPD in a murine model with new molecular mechanisms.

scholarly journals Swyer-James-MacLeod Syndrome: A case report in an adult and review of the literature

2018 ◽  
Vol 5 (4) ◽  
pp. 23
Author(s):  
Eduardo Lening Trejo ◽  
Christian T. Le ◽  
Gary Weinstein ◽  
Patrick Barr ◽  
Mark Feldman
Keyword(s):  
Pulmonary Arteries ◽  
Delayed Diagnosis ◽  
Lower Lobe ◽  
Lung Parenchyma ◽  
Pulmonary Vasculature ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Unilateral Lung Disease ◽  
Pulmonary Parenchyma ◽  
Tract Infections

Swyer-James-MacLeod Syndrome (SJMS) is a rare, unilateral lung disease represented by radiographic translucency of the lung parenchyma secondary to the diminution of the pulmonary vasculature and to the overdistention of the alveoli. It is an uncommon sequela of post-infectious bronchiolitis obliterans (BO) in childhood. Patients with SJMS are often diagnosed in childhood and typically present with recurrent respiratory tract infections. Symptoms during childhood can be mild or absent, leading to a delayed diagnosis in adulthood. SJMS is characterized by the destruction of the small bronchioles and agenesis or hypoplasia of the pulmonary arteries leading to hypoperfusion of the pulmonary parenchyma, resulting in characteristic chest imaging findings of unilateral hyperlucency or translucence.Swyer and James first described this syndrome in 1953. It is a rare disease that can be can be caused by an infection with adenoviruses (types 3, 7, or 21) or Bordetella pertussis, a foreign body in the airway and hydrocarbon inhalation. We present a case of SJMS in whom the adult patient had been misdiagnosed with chronic obstructive pulmonary disease (COPD). She was eventually diagnosed with SJMS based on chest x-ray and chest CT findings of unilateral lung hyperlucency, as well as with scintigraphic findings showing virtually absent perfusion to the left lower lobe of the lung.

Vasoactive mediators and pulmonary hypertension after cigarette smoke exposure in the guinea pig

2006 ◽  
Vol 100 (2) ◽  
pp. 672-678 ◽  
Author(s):  
Joanne L. Wright ◽  
Hsin Tai ◽  
Andrew Churg
Keyword(s):  
Gene Expression ◽  
Nitric Oxide ◽  
Arterial Pressure ◽  
Cigarette Smoke ◽  
Pulmonary Arterial Pressure ◽  
Smoke Exposure ◽  
Cigarette Smoke Exposure ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Pulmonary Arterial

The pathogenesis of pulmonary hypertension in patients with chronic obstructive pulmonary disease is not understood. We have previously shown increased levels of mediators that control vasoconstriction (endothelin-1), vascular cell proliferation (endothelin-1 and vascular endothelial growth factor), and vasodilation (endothelial nitric oxide synthase) in the intrapulmonary arteries of animals exposed to cigarette smoke. To determine whether these mediators could be implicated in the structural remodeling of the arterial vasculature and increased pulmonary arterial pressure caused by chronic cigarette smoke exposure, guinea pigs were exposed to daily cigarette smoke for 6 mo. Pulmonary arterial pressures were measured. Intrapulmonary artery structure was analyzed by morphometry, artery mediator protein expression by immunohistochemistry, and artery mediator gene expression by laser capture microdissection and real-time RT-PCR. We found that the smoke-exposed animals developed increases in pulmonary arterial pressure and increased muscularization of the small pulmonary arteries. Gene expression and protein levels of all three mediators were increased, and pulmonary arterial pressure correlated both with the levels of mediator production and with the degree of arterial muscularization. We conclude that chronic smoke exposure produces increased vasoactive mediator expression in the small intrapulmonary arteries and that these mediators are associated with vascular remodeling as well as increased pulmonary arterial pressure. These findings support the idea that hypertension in chronic obstructive pulmonary disease is a result of direct cigarette smoke-mediated effects on the vasculature and suggest that interference with endothelin and VEGF production and activity or augmentation of nitric oxide levels may be beneficial.

scholarly journals LncRNA Nqo1-AS1 Attenuates Cigarette Smoke-Induced Oxidative Stress by Upregulating its Natural Antisense Transcript Nqo1

2021 ◽  
Vol 12 ◽  
Author(s):  
Haiyun Zhang ◽  
Ruijuan Guan ◽  
Zili Zhang ◽  
Defu Li ◽  
Jingyi Xu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cigarette Smoke ◽  
Mrna Stability ◽  
Molecular Mechanisms ◽  
Antisense Transcript ◽  
Alveolar Epithelium ◽  
Chronic Obstructive ◽  
Protein Coding ◽  
Obstructive Pulmonary Disease ◽  
Coding Potential

Evidence of the involvement of long noncoding RNAs (lncRNAs) in the pathogenesis of chronic obstructive pulmonary disease (COPD) is growing but still largely unknown. This study aims to explore the expression, functions and molecular mechanisms of Fantom3_F830212L20, a lncRNA that transcribes in an antisense orientation to Nqo1.We name this lncRNA as Nqo1 antisense transcript 1 (Nqo1-AS1). The distribution, expression level and protein coding potential of Nqo1-AS1 were determined. The effects of Nqo1-AS1 on cigarette smoke (CS)-induced oxidative stress were also evaluated. The results showed that Nqo1-AS1 were mainly located in the cytoplasm of mouse alveolar epithelium and had a very low protein coding potential. Nqo1-AS1 (or its human homologue) was increased with the increase of CS exposure. Nqo1-AS1 overexpression enhanced the mRNA and protein levels of Nqo1 and Serpina1 mRNA expression, and attenuated CS-induced oxidative stress, whereas knockdown of Nqo1-AS1 significantly decreased Nqo1 and Serpina1 mRNA expressions, and aggravated CS-induced oxidative stress. Nqo1-AS1 increased Nqo1 mRNA stability and upregulated Nqo1 expression through antisense pairing with Nqo1 3′UTR. In conclusion, these results suggest that Nqo1-AS1 attenuates CS-induced oxidative stress by increasing Nqo1 mRNA stability and upregulating Nqo1 expression, which might serve as a novel approach for the treatment of COPD.

Cigarette smoke-mediated inflammatory and oxidative responses are strain-dependent in mice

2008 ◽  
Vol 294 (6) ◽  
pp. L1174-L1186 ◽  
Author(s):  
Hongwei Yao ◽  
Indika Edirisinghe ◽  
Saravanan Rajendrasozhan ◽  
Se-Ran Yang ◽  
Samuel Caito ◽  
...  
Keyword(s):  
Cigarette Smoke ◽  
Mouse Models ◽  
Molecular Mechanisms ◽  
Mouse Strains ◽  
Chronic Obstructive ◽  
Susceptible Mouse ◽  
Obstructive Pulmonary Disease ◽  
Resistant Mouse ◽  
Strain Dependent ◽  
Oxidative Responses

A variety of mouse models have been used to study the pathogenesis of pulmonary emphysema/chronic obstructive pulmonary disease. The effect of cigarette smoke (CS) is believed to be strain dependent, because certain mouse strains are more susceptible or resistant to development of emphysema. However, the molecular basis of susceptibility of mouse strains to effects of CS is not known. We investigated the effect of CS on lungs of most of the commonly used mouse strains to study the molecular mechanism of susceptibility to effects of CS. C57BL/6J, A/J, AKR/J, CD-1, and 129SvJ mice were exposed to CS for 3 consecutive days, and various parameters of inflammatory and oxidative responses were assessed in lungs of these mice. We found that the C57BL/6J strain was highly susceptible, the A/J, AKR/J, and CD-1 strains were moderately susceptible, and the 129SvJ strain was resistant to lung inflammatory and oxidant responses to CS exposure. The mouse strain that was more susceptible to effects of CS showed augmented lung inflammatory cell influx, activation of NF-κB and p38 MAPK, and increased levels of matrix metalloproteinase-9 and NF-κB-dependent proinflammatory cytokines compared with resistant mouse strains. Similarly, decreased levels of glutathione were associated with increased levels of lipid peroxidation products in susceptible mouse strains compared with resistant strains. Hence, we identified the susceptible and resistant mouse strains on the basis of the pattern of inflammatory and oxidant responses. Identification of sensitive and resistant mouse strains could be useful for studying the molecular mechanisms of effects of CS on inflammation and pharmacological interventional studies in CS-exposure mouse models.

scholarly journals Loss of IL-33 enhances elastase-induced and cigarette smoke extract-induced emphysema in mice

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Daisuke Morichika ◽  
Akihiko Taniguchi ◽  
Naohiro Oda ◽  
Utako Fujii ◽  
Satoru Senoo ◽  
...  
Keyword(s):  
Cigarette Smoke ◽  
Intratracheal Instillation ◽  
Inflammatory Cells ◽  
Cigarette Smoke Extract ◽  
Lymphoid Cells ◽  
Chronic Obstructive ◽  
Porcine Pancreas ◽  
Obstructive Pulmonary Disease ◽  
Quantitative Morphometry ◽  
Cytokines And Chemokines

Abstract Background IL-33, which is known to induce type 2 immune responses via group 2 innate lymphoid cells, has been reported to contribute to neutrophilic airway inflammation in chronic obstructive pulmonary disease. However, its role in the pathogenesis of emphysema remains unclear. Methods We determined the role of interleukin (IL)-33 in the development of emphysema using porcine pancreas elastase (PPE) and cigarette smoke extract (CSE) in mice. First, IL-33−/− mice and wild-type (WT) mice were given PPE intratracheally. The numbers of inflammatory cells, and the levels of cytokines and chemokines in the bronchoalveolar lavage (BAL) fluid and lung homogenates, were analyzed; quantitative morphometry of lung sections was also performed. Second, mice received CSE by intratracheal instillation. Quantitative morphometry of lung sections was then performed again. Results Intratracheal instillation of PPE induced emphysematous changes and increased IL-33 levels in the lungs. Compared to WT mice, IL-33−/− mice showed significantly greater PPE-induced emphysematous changes. No differences were observed between IL-33−/− and WT mice in the numbers of macrophages or neutrophils in BAL fluid. The levels of hepatocyte growth factor were lower in the BAL fluid of PPE-treated IL-33−/− mice than WT mice. IL-33−/− mice also showed significantly greater emphysematous changes in the lungs, compared to WT mice, following intratracheal instillation of CSE. Conclusion These observations suggest that loss of IL-33 promotes the development of emphysema and may be potentially harmful to patients with COPD.

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