Vitamin E relieves chronic obstructive pulmonary disease by inhibiting COX2-mediated p-STAT3 nuclear translocation through the EGFR/MAPK signaling pathway.

Patients with chronic obstructive pulmonary disease (COPD) are characterized by an imbalance between oxidant enzymes and antioxidant enzymes. In the present study, we explored the protective effect of vitamin E on COPD and the underlying mechanisms. Targets of vitamin E were predicted by bioinformatics analysis. After establishing cigarette smoke (CS)-induced COPD rats, the expression levels of epidermal growth factor receptor (EGFR), cyclooxygenase 2 (COX2), and transcriptional activity of signal transducer and activator of transcription 3 (STAT3) were measured. Additionally, the effects of vitamin E on CS-induced COPD were explored by assessing inflammation, the reactive oxygen species (ROS), the activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA), viability of human bronchial epithelioid (HBE) cells, and the expression of EGFR/MAPK pathway-related factors after loss- and gain- function assays. Vitamin E alleviated COPD. Vitamin E inhibited MAPK signaling pathway through decreasing EGFR expression. Additionally, vitamin E suppressed CS-induced HBE cell damage. Functionally, vitamin E attenuated CS-induced inflammation, apoptosis, and ROS by inhibiting the EGFR/MAPK axis, thereby inhibiting COX2-mediated p-STAT3 nuclear translocation. Moreover, overexpression of COX2 attenuated the protective effect of vitamin E on COPD rats. The present study shows that vitamin E inhibits the expression of COX2 by negatively regulating the EGFR/MAPK pathway, thereby inhibiting the translocation of phosphorylated STAT3 to the nucleus and relieving COPD.

Cpt1a alleviates cigarette smoke­induced chronic obstructive pulmonary disease.

The current study aimed to determine the expression of carnitine palmitoyltransferase 1A (Cpt1a) in the lung tissue of chronic obstructive pulmonary disease (COPD) patients and its correlation with lung function. An increase in Cpt1a expression improved lung function in patients with COPD by inhibiting apoptosis and the inflammatory response of lung endothelial cells. Lung tissues of 20 patients with COPD and 10 control patients were collected, their Cpt1a expression was determined by western blotting and apoptosis and inflammation were assessed by haematoxylin-eosin staining, TUNEL assay and ELISA. Mice with knockout or overexpression of Cpt1a were constructed by lentivirus in vivo. A COPD model was induced by cigarette smoke and the role of Cpt1a in COPD was determined in vivo and in vitro. Cpt1a expression was positively correlated with lung function and negatively correlated with apoptosis and inflammation. Patients with COPD with higher expression of Cpt1a in lung tissues had improved lung function indices and lung tissue morphology with less apoptosis and decreased inflammatory response. Compared with the control group, COPD mice with Cpt1a knockdown had aggravated lung dysfunction and increased lung inflammation and apoptosis. Overexpression of Cpt1a alleviated lung dysfunction and reduced inflammatory response and apoptosis of lung tissues in COPD mice. Pulmonary microvascular endothelial cells of mice were isolated in vitro and the results were consistent with the findings obtained in vivo. In conclusion, the clinical, in vivo and in vitro data confirmed for the first time that Cpt1a alleviated lung dysfunction of patients with COPD by inhibiting apoptosis of endothelial cells and inflammatory responses.

Cigarette Smoke Reduces Fatty Acid Catabolism, Leading to Apoptosis in Lung Endothelial Cells: Implication for Pathogenesis of COPD.

Endothelial cell (EC) apoptosis contributes to cigarette smoke (CS)-induced pulmonary emphysema. Metabolism of glucose, glutamine, and fatty acid is dysregulated in patients with chronic obstructive pulmonary disease (COPD). Whether CS causes metabolic dysregulation in ECs leading to development of COPD remains elusive. We hypothesized that CS alters metabolism, resulting in apoptosis in lung ECs. To test this hypothesis, we treated primary mouse pulmonary microvascular ECs (PMVECs) with CS extract (CSE) and employed PMVECs from healthy subjects and COPD patients. We found that mitochondrial respiration was reduced in CSE-treated PMVECs and in PMVECs from COPD patients. Specifically, oxidation of fatty acids (FAO) was reduced in these cells, which linked to reduced carnitine palmitoyltransferase 1a (Cpt1a), an essential enzyme for carnitine shuttle. CSE-induced apoptosis was further increased when cells were treated with a specific Cpt1 inhibitor etomoxir or transfected with Cpt1a siRNA. L-Carnitine treatment augmented FAO but attenuated CSE-induced apoptosis by upregulating Cpt1a. CSE treatment increased palmitate-derived ceramide synthesis, which was reduced by L-carnitine. Although CSE treatment increased glycolysis, inhibiting glycolysis with 2-deoxy-d-glucose had no effects on CSE-mediated apoptosis in lung ECs. Conclusively, FAO reduction increases ceramide and apoptosis in lung ECs treated with CSE, which may contribute to the pathogenesis of COPD/emphysema.

Postoperative outcomes of patients with chronic obstructive pulmonary disease undergoing coronary artery bypass grafting surgery: A meta-analysis.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a frequent comorbid disease in patients undergoing coronary artery bypass grafting (CABG) surgery, with an incidence ranging from 4% to 20.5%. Conventionally, COPD was recognized as a surgical contraindication to CABG. Because of the recent improvements in surgical techniques, anesthesia, and postoperative management, CABG has been performed more commonly in patients with COPD. However, studies have shown the various effects of COPD on postoperative morbidity and mortality after CABG, and this remains to be well defined. OBJECTIVES: To compare the postoperative outcomes after CABG between patients with and those without COPD. METHODS: A systematic search was conducted in the Cochrane Library, PubMed, EmBase, and Ovid databases (until May 10, 2018). Studies comparing perioperative results and mortality outcomes after CABG between patients with and those without COPD were evaluated independently by 2 reviewers to identify the potentially eligible studies. Review Manager and STATA software were used for statistical analyses. RESULTS: No significant difference in the mortality rates were found between patients with and those without COPD. COPD was associated with a higher respiratory failure rate (odds ratio [OR] = 4.01; 95% CI: 1.19-13.51, P = .03; P <.001 for heterogeneity), higher pneumonia rate (OR = 2.92; 95% CI: 2.37-3.60, P <.00001; P = .73 for heterogeneity), higher stroke rate (OR = 2.91; 95% CI: 1.37-6.18, P = .005; P = .60 for heterogeneity), higher renal failure rate (OR = 1.60; 95% CI: 1.30-1.97, P <.00001; P = .19 for heterogeneity), and higher wound infection rate (OR = 2.16; 95% CI: 1.21-3.88, P = .01; P = .53 for heterogeneity) after CABG. CONCLUSIONS: Patients with COPD were at higher risks for developing postoperative morbidities, particularly pneumonia, respiratory failure, stroke, renal failure, and wound infection. Although COPD was not associated with a higher risk of mortality, caution should be taken when a patient with COPD is indicated for CABG, considering the higher odds of postoperative complications involving the respiratory system and others.