Ticagrelor Increases SIRT1 and HES1 mRNA Levels in Peripheral Blood Cells from Patients with Stable Coronary Artery Disease and Chronic Obstructive Pulmonary Disease

Ticagrelor is a powerful P2Y12 inhibitor with pleiotropic effects in the cardiovascular system. Consistently, we have reported that in patients with stable coronary artery disease (CAD) and concomitant chronic obstructive pulmonary disease (COPD) who underwent percutaneous coronary intervention (PCI), 1-month treatment with ticagrelor was superior in improving biological markers of endothelial function, compared with clopidogrel. The objective of this study was to investigate the mechanisms underlying these beneficial effects of ticagrelor by conducting molecular analyses of RNA isolated from peripheral blood cells of these patients. We determined mRNAs levels of markers of inflammation and oxidative stress, such as RORγt (T helper 17 cells marker), FoxP3 (regulatory T cells marker), NLRP3, ICAM1, SIRT1, Notch ligands JAG1 and DLL4, and HES1, a Notch target gene. We found that 1-month treatment with ticagrelor, but not clopidogrel, led to increased levels of SIRT1 and HES1 mRNAs. In patients treated with ticagrelor or clopidogrel, we observed a negative correlation among changes in both SIRT1 and HES1 mRNA and serum levels of Epidermal Growth Factor (EGF), a marker of endothelial dysfunction found to be reduced by ticagrelor treatment in our previous study. In conclusion, we report that in stable CAD/COPD patients ticagrelor positively regulates HES1 and SIRT1, two genes playing a protective role in the context of inflammation and oxidative stress. Our observations confirm and expand previous studies showing that the beneficial effects of ticagrelor in stable CAD/COPD patients may be, at least in part, mediated by its capacity to reduce systemic inflammation and oxidative stress.

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Oxidative stress and damage to erythrocytes in patients with chronic obstructive pulmonary disease — changes in ATPase and acetylcholinesterase activity

Biochemistry and Cell Biology ◽

10.1139/bcb-2015-0066 ◽

2015 ◽

Vol 93 (6) ◽

pp. 574-580 ◽

Cited By ~ 11

Author(s):

Bożena Bukowska ◽

Paulina Sicińska ◽

Aneta Pająk ◽

Aneta Koceva-Chyla ◽

Tadeusz Pietras ◽

...

Keyword(s):

Oxidative Stress ◽

Chronic Obstructive Pulmonary Disease ◽

Red Blood Cells ◽

Pulmonary Disease ◽

Blood Cells ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Membrane Enzymes ◽

Copd Patients ◽

The Impact

The study indicates, for the first time, the changes in both ATPase and AChE activities in the membrane of red blood cells of patients diagnosed with COPD. Chronic obstructive pulmonary disease (COPD) is one of the most common and severe lung disorders. We examined the impact of COPD on redox balance and properties of the membrane of red blood cells. The study involved 30 patients with COPD and 18 healthy subjects. An increase in lipid peroxidation products and a decrease in the content of -SH groups in the membrane of red blood cells in patients with COPD were observed. Moreover, an increase in the activity of glutathione peroxidase and a decrease in superoxide dismutase, but not in catalase activity, were found as well. Significant changes in activities of erythrocyte membrane enzymes in COPD patients were also evident demonstrated by a considerably lowered ATPase activity and elevated AChE activity. Changes in the structure and function of red blood cells observed in COPD patients, together with changes in the activity of the key membrane enzymes (ATPases and AChE), can result from the imbalance of redox status of these cells due to extensive oxidative stress induced by COPD disease.

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Increased Serum ox-LDL Levels Correlated with Lung Function, Inflammation, and Oxidative Stress in COPD

Mediators of Inflammation ◽

10.1155/2013/972347 ◽

2013 ◽

Vol 2013 ◽

pp. 1-5 ◽

Cited By ~ 17

Author(s):

Yongchun Shen ◽

Ting Yang ◽

Shujin Guo ◽

Xiao'ou Li ◽

Lei Chen ◽

...

Keyword(s):

Oxidative Stress ◽

Lung Function ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Serum Levels ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Stress Studies ◽

Copd Patients ◽

And Oxidative Stress

Chronic obstructive pulmonary disease (COPD) is associated with abnormal inflammation and high oxidative stress. Studies suggest that oxidized low density lipoprotein (ox-LDL) is involved in diseases associated with oxidative stress and inflammation. However, no data on the possible relationship between COPD and ox-LDL are available. This study compared serum levels of ox-LDL in 48 COPD patients and 32 health controls and correlated them with lung function, systematic inflammation, and oxidative stress. Serum levels of ox-LDL, C-reactive protein (CRP), and oxidative stress (measured by reactive oxygen species, ROS) were analyzed using commercial kits. Mean levels of serum ox-LDL were significantly higher in COPD patients than in controls (18.62±7.56versus12.57±5.90 mU/L,P<0.05). Serum levels of CRP and ROS were also significantly higher in COPD patients. Serum levels of ox-LDL in COPD patients correlated inversely with FEV1% predicted, an index of lung function (r=−0.347,P=0.016), while they correlated positively with CRP and ROS levels. These results suggest that serum levels of ox-LDL are increased in COPD patients and that these levels are associated with lung function, inflammation, and oxidative stress in COPD. Future studies are needed to determine whether and how ox-LDL plays a role in COPD.

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Methylation of SERPINA1 gene promoter may predict chronic obstructive pulmonary disease in patients affected by acute coronary syndrome

Clinical Epigenetics ◽

10.1186/s13148-021-01066-w ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

John Charles Rotondo ◽

Giorgio Aquila ◽

Lucia Oton-Gonzalez ◽

Rita Selvatici ◽

Paola Rizzo ◽

...

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Acute Coronary Syndrome ◽

Pulmonary Disease ◽

Blood Cells ◽

Gene Promoter ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Coronary Syndrome ◽

Copd Patients ◽

Potential Biomarker

Abstract Background Diagnostic biomarkers for detecting chronic obstructive pulmonary disease (COPD) in acute coronary syndrome (ACS) patients are not available. SERPINA1, coding for the most potent circulating anti-inflammatory protein in the lung, has been found to be differentially methylated in blood cells from COPD patients. This study aimed to investigate the methylation profile of SERPINA1 in blood cells from ACS patients, with (COPD+) or without COPD (COPD−). Methods Blood samples were from 115 ACS patients, including 30 COPD+ and 85 COPD− according to lung function phenotype, obtained with spirometry. DNA treated with sodium bisulfite was PCR-amplified at SERPINA1 promoter region. Methylation analysis was carried out by sequencing the PCR products. Lymphocytes count in ACS patients was recorded at hospital admission and discharge. Results SERPINA1 was hypermethylated in 24/30 (80%) COPD+ and 48/85 (56.5%) COPD− (p < 0.05). Interestingly, at hospital discharge, lymphocytes count was higher in COPD− patients carrying SERPINA1 hypermethylated (1.98 × 103 ± 0.6 cell/µl) than in COPD− carrying SERPINA1 hypomethylated (1.7 × 103 ± 0.48 cell/µl) (p < 0.05). Conclusions SERPINA1 is hypermethylated in blood cells from COPD+ patients. COPD− carrying SERPINA1 hypermethylated and high lymphocytes count may be at risk of COPD development. Therefore, SERPINA1 hypermethylation may represent a potential biomarker for predicting COPD development in ACS patients.

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High Vegetables Intake and Response to COPD Rehabilitation. The Role of Oxidative Stress, Inflammation and Dna Damage.

10.20944/preprints202106.0558.v1 ◽

2021 ◽

Author(s):

Sara Ilari ◽

Laura Vitiello ◽

Patrizia Russo ◽

Stefania Proietti ◽

Mirta Milic ◽

...

Keyword(s):

Oxidative Stress ◽

Dna Damage ◽

Pulmonary Rehabilitation ◽

Vegetable Consumption ◽

Natural Antioxidants ◽

Lung Parenchyma ◽

Normal Diet ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Copd Patients

Chronic obstructive pulmonary disease (COPD) is a respiratory disease associated with airways inflammation and lung parenchyma fibrosis. The primary goals of COPD treatment are to re-duce symptoms and risk of exacerbations, therefore pulmonary rehabilitation is considered the key component of managing COPD patients. Oxidative airway damage, inflammation and re-duction of endogenous antioxidant enzymes are known to play a crucial role in the pathogenesis of COPD. Natural antioxidants have also recently been considered as they play an important role in metabolism, DNA repair and fighting the effects of oxidative stress. In this paper we evaluated the response of 105 elderly COPD patients to pulmonary rehabilitation (PR), based on high or low vegetable consumption, by analyzing clinical parameters and biological measure-ments at baseline and after completion of the three weeks PR. We found that high vegetable in-take in normal diet, without any specific intervention, can increase the probability to success-fully respond to rehabilitation (65.4% of responders ate vegetables daily vs. 40.0% of Non-Responders, p=0.033). Three weeks of pulmonary rehabilitation are probably too short to reveal a reduction of the oxidative stress and DNA damage, but are enough to show an im-provement in the patient's inflammatory state.

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Fiber atrophy, oxidative stress, and oxidative fiber reduction are the attributes of different phenotypes in chronic obstructive pulmonary disease patients

Journal of Applied Physiology ◽

10.1152/japplphysiol.00778.2013 ◽

2013 ◽

Vol 115 (12) ◽

pp. 1796-1805 ◽

Cited By ~ 11

Author(s):

Fares Gouzi ◽

Aldjia Abdellaoui ◽

Nicolas Molinari ◽

Edith Pinot ◽

Bronia Ayoub ◽

...

Keyword(s):

Oxidative Stress ◽

Chronic Obstructive Pulmonary Disease ◽

Pulmonary Disease ◽

Muscle Protein ◽

Statistical Significance ◽

Chronic Obstructive ◽

Type I ◽

Obstructive Pulmonary Disease ◽

Peripheral Muscle ◽

Copd Patients

Peripheral muscle dysfunction, associated with reductions in fiber cross-sectional area (CSA) and in type I fibers, is a key outcome in chronic obstructive pulmonary disease (COPD). However, COPD peripheral muscle function and structure show great heterogeneity, overlapping those in sedentary healthy subjects (SHS). While discrepancies in the link between muscle structure and phenotype remain unexplained, we tested whether the fiber CSA and the type I fiber reductions were the attributes of different phenotypes of the disease, using unsupervised clustering method and post hoc validation. Principal component analysis performed on functional and histomorphological parameters in 64 COPD patients {forced expiratory volume in 1 s (FEV1) = 42.0 [30.0–58.5]% predicted} and 27 SHS (FEV1 = 105.0 [95.0–114.0]% predicted) revealed two COPD clusters with distinct peripheral muscle dysfunctions. These two clusters had different type I fiber proportion (26.0 ± 14.0% vs. 39.8 ± 12.6%; P < 0.05), and fiber CSA (3,731 ± 1,233 vs. 5,657 ± 1,098 μm2; P < 0.05). The “atrophic” cluster showed an increase in muscle protein carbonylation (131.5 [83.6–200.3] vs. 83.0 [68.3–105.1]; P < 0.05). Then, COPD patients underwent pulmonary rehabilitation. If the higher risk of exacerbations in the “atrophic” cluster did not reach statistical significance after adjustment for FEV1 (hazard ratio: 2.43; P = 0.11, n = 54), the improvement of VO2sl after training was greater than in the nonatrophic cluster (+24 ± 16% vs. +6 ± 13%; P < 0.01). Last, their age was similar (60.4 ± 8.8 vs. 60.8 ± 9.0 yr; P = 0.87), suggesting a different time course of the disease. We identified and validated two phenotypes of COPD patients showing different muscle histomorphology and level of oxidative stress. Thus our study demonstrates that the muscle heterogeneity is the translation of different phenotypes of the disease.

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Biological effects of ticagrelor over clopidogrel in patients with stable coronary artery disease and chronic obstructive pulmonary disease

Thrombosis and Haemostasis ◽

10.1160/th16-12-0973 ◽

2017 ◽

Vol 117 (06) ◽

pp. 1208-1216 ◽

Cited By ~ 26

Author(s):

Gianluca Campo ◽

Francesco Vieceli Dalla Sega ◽

Rita Pavasini ◽

Giorgio Aquila ◽

Francesco Gallo ◽

...

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Endothelial Function ◽

Pulmonary Disease ◽

Primary Endpoint ◽

Stable Coronary Artery Disease ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Artery Disease

SummaryPatients with SCAD and concomitant COPD are at high risk of cardiovascular adverse events, due to chronic inflammation, responsible of endothelial dysfunction, oxidative stress and heightened platelet reactivity (PR). The objective of this randomised clinical trial was to test if ticagrelor is superior to clopidogrel in improving endothelial function in patients with stable coronary artery disease (SCAD) and concomitant chronic obstructive pulmonary disease (COPD). Forty-six patients with SCAD and COPD undergoing percutaneous coronary intervention (PCI) were randomly assigned to receive clopidogrel (n=23) or ticagrelor (n=23) on top of standard therapy with aspirin. The following parameters were assessed at baseline and after 1 month: i) rate of apoptosis and ii) nitric oxide (NO) levels in human umbilical vein endothelial cells (HUVECs), iii) levels of reactive oxygen species (ROS) in peripheral blood mononuclear cell, iv) 29 cytokines/chemokines, v) on-treatment PR. The primary endpoint of the study was the 1-month rate of HUVECs apoptosis. The rate of apoptosis after 1 month was significantly lower in patients treated with ticagrelor (7.4 ± 1.3% vs 9.3 ± 1.5%, p<0.001), satisfying the pre-specified primary endpoint. In the ticagrelor arm, levels of NO were higher (10.1 ± 2.2 AU vs 8.5 ± 2.6 AU, p=0.03) while those of ROS (4 ± 1.8 AU vs 5.7 ± 2.8 AU, p=0.02) and P2Y12 reactivity units (52 ± 70 PRU vs 155 ± 62 PRU, p<0.001) were lower. There were no differences in cytokines/chemokines levels and aspirin reactivity units between groups. In patients with SCAD and COPD undergoing PCI, ticagrelor, as compared to clopidogrel is superior in improving surrogate markers of endothelial function and on-treatment PR (ClinicalTrials.gov, NCT02519608).Supplementary Material to this article is available online at www.thrombosis-online.com.

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COPD and stroke: are systemic inflammation and oxidative stress the missing links?

Clinical Science ◽

10.1042/cs20160043 ◽

2016 ◽

Vol 130 (13) ◽

pp. 1039-1050 ◽

Cited By ~ 61

Author(s):

Victoria Austin ◽

Peter J. Crack ◽

Steven Bozinovski ◽

Alyson A. Miller ◽

Ross Vlahos

Keyword(s):

Oxidative Stress ◽

Risk Factors ◽

Systemic Inflammation ◽

Vascular Dysfunction ◽

Airflow Limitation ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Cardiovascular Comorbidities ◽

Shared Risk ◽

And Oxidative Stress

Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation and loss of lung function, and is currently the third largest cause of death in the world. It is now well established that cardiovascular-related comorbidities such as stroke contribute to morbidity and mortality in COPD. The mechanisms linking COPD and stroke remain to be fully defined but are likely to be interconnected. The association between COPD and stroke may be largely dependent on shared risk factors such as aging and smoking, or the association of COPD with traditional stroke risk factors. In addition, we propose that COPD-related systemic inflammation and oxidative stress may play important roles by promoting cerebral vascular dysfunction and platelet hyperactivity. In this review, we briefly discuss the pathogenesis of COPD, acute exacerbations of COPD (AECOPD) and cardiovascular comorbidities associated with COPD, in particular stroke. We also highlight and discuss the potential mechanisms underpinning the link between COPD and stroke, with a particular focus on the roles of systemic inflammation and oxidative stress.

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Effect of Spirulina Intervention on Oxidative Stress, Antioxidant Status, and Lipid Profile in Chronic Obstructive Pulmonary Disease Patients

BioMed Research International ◽

10.1155/2015/486120 ◽

2015 ◽

Vol 2015 ◽

pp. 1-7 ◽

Cited By ~ 23

Author(s):

Md. Ismail ◽

Md. Faruk Hossain ◽

Arifur Rahman Tanu ◽

Hossain Uddin Shekhar

Keyword(s):

Oxidative Stress ◽

Chronic Obstructive Pulmonary Disease ◽

Lipid Profile ◽

Pulmonary Disease ◽

Antioxidant Status ◽

Lipid Hydroperoxide ◽

Blood Parameters ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Copd Patients

Background and Objective.Oxidative stress is intimately associated with many diseases, including chronic obstructive pulmonary disease (COPD). Study objectives include a comparison of the oxidative stress, antioxidant status, and lipid profile between COPD patients and controls and evaluation of the effect of spirulina intervention on oxidative stress, antioxidant status, and lipid profile of COPD patients.Methods.30 patients with COPD and 20 controls with no respiratory problems were selected. Global Initiative for Chronic Obstructive Lung Disease criteria were served as the basis of COPD diagnosis. The serum content of malondialdehyde (MDA), lipid hydroperoxide, glutathione (GSH), vitamin C, cholesterol, triglyceride (TG), and high density lipoprotein (HDL) was measured. The activity of superoxide dismutase (SOD), catalase (CAT), and glutathione-s-transferase (GST) was also measured. Two different doses, (500 × 2) mg and (500 × 4) mg spirulina, were given to two groups, each of which comprises 15 COPD patients.Results.All targeted blood parameters have significant difference(P=0.000)between COPD patients and controls except triglyceride (TG). Spirulina intake for 30 and 60 days at (500 × 2) mg dose has significantly reduced serum content of MDA, lipid hydroperoxide, and cholesterol(P=0.000)while increasing GSH, Vit C level(P=0.000), and the activity of SOD(P=0.000)and GST(P=0.038). At the same time, spirulina intake for 30 and 60 days at (500 × 4) mg dose has favorable significant effect(P=0.000)on all targeted blood parameters except for HDL(P=0.163).

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Impaired training-induced angiogenesis process with loss of pericyte-endothelium interactions is associated with an abnormal capillary remodelling in the skeletal muscle of COPD patients

Respiratory Research ◽

10.1186/s12931-019-1240-6 ◽

2019 ◽

Vol 20 (1) ◽

Cited By ~ 2

Author(s):

Léo Blervaque ◽

Emilie Passerieux ◽

Pascal Pomiès ◽

Matthias Catteau ◽

Nelly Héraud ◽

...

Keyword(s):

Oxidative Stress ◽

Skeletal Muscle ◽

Exercise Training ◽

Exercise Intolerance ◽

Moderate Intensity ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Link Type ◽

Copd Patients ◽

Response To Exercise

Abstract Chronic obstructive pulmonary disease (COPD) is associated with exercise intolerance and limits the functional gains in response to exercise training in patients compared to sedentary healthy subjects (SHS). The blunted skeletal muscle angiogenesis previously observed in COPD patients has been linked to these limited functional improvements, but its underlying mechanisms, as well as the potential role of oxidative stress, remain poorly understood. Therefore, we compared ultrastructural indexes of angiogenic process and capillary remodelling by transmission electron microscopy in 9 COPD patients and 7 SHS after 6 weeks of individualized moderate-intensity endurance training. We also assessed oxidative stress by plasma-free and esterified isoprostane (F2-IsoP) levels in both groups. We observed a capillary basement membrane thickening in COPD patients only (p = 0.008) and abnormal variations of endothelial nucleus density in response to exercise training in these patients when compared to SHS (p = 0.042). COPD patients had significantly fewer occurrences of pericyte/endothelium interdigitations, a morphologic marker of capillary maturation, than SHS (p = 0.014), and significantly higher levels of F2-IsoP (p = 0.048). Last, the changes in pericyte/endothelium interdigitations and F2-IsoP levels in response to exercise training were negatively correlated (r = − 0.62, p = 0.025). This study is the first to show abnormal capillary remodelling and to reveal impairments during the whole process of angiogenesis (capillary creation and maturation) in COPD patients. Trial registration NCT01183039 & NCT01183052, both registered 7 August 2010 (retrospectively registered).

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