Cigarette Smoke Directly Promotes Pulmonary Arterial Remodeling and Kv7.4 Channel Dysfunction

Sevilla-Montero, Javier; Labrousse-Arias, David; Fernández-Pérez, Cristina; Fernández-Blanco, L; Barreira, Bianca; Mondéjar-Parreño, Gema; Alfaro‐Arnedo, Elvira; López, Icíar P.; Pérez-Rial, Sandra; Peces-Barba, Germán; Pichel, José G.; Peinado, Víctor I.; Cogolludo, Ángel; Calzada, Marı́a J.

doi:10.1164/rccm.201911-2238oc

Cited by 25 publications

(24 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Even after revascularization in patients with complex coronary artery disease, smoke predicts poor clinical outcomes during 5-year follow-up ( 12 ). Besides, smoke directly contributes to pulmonary arterial remodeling through increased cell senescence ( 13 ), which will further exacerbate right heart dysfunction once exposed to high altitude. This is probably because smoke could induce vascular and systemic inflammatory response, aggravate coronary endothelial injury, and cause vasomotor dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Correlation Between Neutrophil to Lymphocyte Ratio and Myocardial Injury in Population Exposed to High Altitude

He¹,

He²,

Yang³

et al. 2021

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

Objective: Myocardial injury is a severe complication in population exposed to high altitude. As a new biomarker for inflammatory response, neutrophil to lymphocyte ratio (NLR) has been widely used to predict the prognosis of various diseases. In this study, we intend to explore the risk factors for myocardial injury at high altitude and examine the relationship between NLR level and development of myocardial injury.Methods: Consecutive patients admitted to a secondary general hospital at high altitude from June 2019 to May 2020 were selected into this retrospective study. Clinical and biochemical data were collected. According to the results of lactate dehydrogenase (LDH), creatine kinase (CK), creatine kinase isoenzymes (CK-MB), and aspartate amino transferase (AST), patients were divided into myocardial injury group and normal group.Results: A total of 476 patients were enrolled in this study. Myocardial injury occurred in 158 patients (33.2%). We found that altitude, NLR, hemoglobin, total bilirubin, total cholesterol, and lipoprotein A in myocardial injury group were significantly higher than that in normal group (P < 0.05), while platelet count in myocardial injury group was significantly lower than that in normal group (P < 0.05). Logistic multivariate regression analysis revealed that there was an independent relationship between myocardial injury and smoke, NLR, hemoglobin (P < 0.05). By using Spearman correlation analysis, NLR was proved to have a significant positive correlation with LDH, CK, and CK-MB (P < 0.05) instead of AST. A receiver operating characteristic (ROC) curve was drawn to demonstrate that NLR could significantly predict the occurrence of myocardial injury with an area under the curve (AUC) of 0.594 (95% CI: 0.537–0.650, P < 0.05), and the level of 2.967 (sensitivity = 38.0%, specificity = 83.6%) was optimal cutoff value.Conclusion: The incidence of myocardial injury is high in population at high altitude. Smoke, hemoglobin, and NLR are independent factors related to myocardial injury. As a convenient and efficient marker, NLR is found to be closely associated with myocardial enzymes and have a predict role in the occurrence of myocardial injury. This study will provide a theoretical basis on NLR for the early diagnosis of myocardial injury at high altitude.

show abstract

Section: Discussionmentioning

confidence: 99%

Correlation Between Neutrophil to Lymphocyte Ratio and Myocardial Injury in Population Exposed to High Altitude

He¹,

He²,

Yang³

et al. 2021

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

show abstract

“…It is well known that hypoxia drives pulmonary hypertension (PH) by promoting pulmonary arterial remodelling and dysregulation of voltage-gated K+ channels. Interestingly, Sevilla-Montero et al [36] showed that cigarette smoking contributes to pulmonary arterial remodelling by a process which is facilitated by reducing the expression of KCNK3 and loss of Kv1.5 function in pulmonary artery smooth muscle cells that contributes to dysregulation of K+ channels. This might be a hypoxia-independent event that can be observed in non-COPD smokers.…”

Section: Discussionmentioning

confidence: 99%

Nocturnal Hypoxemia and CT Determined Pulmonary Artery Enlargement in Smokers

Seijó

Divo

Bastarrika

et al. 2021

JCM

View full text Add to dashboard Cite

Background: Pulmonary artery enlargement (PAE) detected using chest computed tomography (CT) is associated with poor outcomes in chronic obstructive pulmonary disease (COPD). It is unknown whether nocturnal hypoxemia occurring in smokers, with or without COPD, obstructive sleep apnoea (OSA) or their overlap, may be associated with PAE assessed by chest CT. Methods: We analysed data from two prospective cohort studies that enrolled 284 smokers in lung cancer screening programs and completing baseline home sleep studies and chest CT scans. Main pulmonary artery diameter (PAD) and the ratio of the PAD to that of the aorta (PA:Ao ratio) were measured. PAE was defined as a PAD ≥ 29 mm in men and ≥27 mm in women or as a PA:Ao ratio > 0.9. We evaluated the association of PAE with baseline characteristics using multivariate logistic models. Results: PAE prevalence was 27% as defined by PAD measurements and 11.6% by the PA:Ao ratio. A body mass index ≥ 30 kg/m2 (OR 2.01; 95%CI 1.06–3.78), lower % predicted of forced expiratory volume in one second (FEV1) (OR 1.03; 95%CI 1.02–1.05) and higher % of sleep time with O2 saturation < 90% (T90) (OR 1.02; 95%CI 1.00–1.03), were associated with PAE as determined by PAD. However, only T90 remained significantly associated with PAE as defined by the PA:Ao ratio (OR 1.02; 95%CI 1.01–1.03). In the subset group without OSA, only T90 remains associated with PAE, whether defined by PAD measurement (OR 1.02; 95%CI 1.01–1.03) or PA:Ao ratio (OR 1.04; 95%CI 1.01–1.07). Conclusions: In smokers with or without COPD, nocturnal hypoxemia was associated with PAE independently of OSA coexistence.

show abstract

“…This suggests that other unknown mechanisms, hypoxiaindependent and directly triggered by CS on the pulmonary vasculature, may also be responsible for PH development on these patients 7 . In fact, our recently published results demonstrate that cigarette smoke extract (CSE) causes a decrease of PA vasoconstriction and vasodilation responses, with alterations intrinsic to the smooth muscle cell (SMC) layer which could contribute to CS-dependent PH development 8 .…”

Section: Introductionmentioning

confidence: 99%

Cigarette smoke induces pulmonary arterial dysfunction through an imbalance in the guanylyl cyclase redox status

Sevilla-Montero

Pino-Fadón

Munar-Rubert

et al. 2022

Preprint

View full text Add to dashboard Cite

Chronic obstructive pulmonary disease (COPD), whose main risk factor is cigarette smoking (CS), is one of the most common diseases globally. Many COPD patients also develop pulmonary hypertension (PH), a severe complication that leads to premature death. Evidence suggests reactive oxygen species (ROS) involvement in COPD and PH, especially regarding pulmonary artery smooth muscle cells (PASMC) dysfunction. However, the effects of CS on the pulmonary vasculature are not completely understood. Herein we provide evidence on the effects of CS extract (CSE) exposure on PASMC regarding ROS production, antioxidant response and its consequences on vascular tone dysregulation. Our results indicate that CSE exposure promotes mitochondrial fission, mitochondrial membrane depolarization and increased mitochondrial superoxide levels. However, the increase in superoxide did not parallel a counterbalancing antioxidant response in human pulmonary artery (PA) cells. Interestingly, the mitochondrial superoxide chelator mitoTEMPO reduced mitochondrial fission and membrane potential depolarization caused by CSE. As we have previously shown, CSE reduces PA vasoconstriction and vasodilation. In this respect, mitoTEMPO prevented the impaired nitric oxide-mediated vasodilation, while vasoconstriction remained reduced. Finally, we observed a CSE-driven downregulation of the Cyb5R3 enzyme, which prevents soluble guanylyl cyclase oxidation in PASMC. This might explain the CSE-mediated decrease in PA vasodilation. These results provide evidence that there might be a connection between mitochondrial ROS and altered vasodilation responses in PH secondary to COPD, and strongly support the potential of antioxidant strategies specifically targeting mitochondria as a new therapy for these diseases.

show abstract

Cigarette Smoke Directly Promotes Pulmonary Arterial Remodeling and Kv7.4 Channel Dysfunction

Cited by 25 publications

References 52 publications

Correlation Between Neutrophil to Lymphocyte Ratio and Myocardial Injury in Population Exposed to High Altitude

Correlation Between Neutrophil to Lymphocyte Ratio and Myocardial Injury in Population Exposed to High Altitude

Nocturnal Hypoxemia and CT Determined Pulmonary Artery Enlargement in Smokers

Cigarette smoke induces pulmonary arterial dysfunction through an imbalance in the guanylyl cyclase redox status

Contact Info

Product

Resources

About