Growing global use of heat-not-burn cigarettes (HNBC) prompts investigation. Prior studies assessed HNBC's effects on cardiovascular health, revealing heightened oxidative stress, platelet activation, and endothelial dysfunction. However, limited understanding exists regarding passive smoking's impact on children exposed to HNBC. This study aims to assess levels of oxidative stress, endothelial and platelet function among children exposed to passive smoke from HNBC, traditional tobacco (TT) cigarettes and unexposed subjects. Seventy-eight children (2–18 years) were divided into three groups: HNBC passive smokers (n = 26), TT cigarette exposed (n = 26), and control (CNT) group (n = 26, unexposed). Oxidative stress was evaluated by serum NADPH oxidase-2 (NOX2) activity, assessed by soluble Nox2-derived peptide (sNOX2-dp), isoprostanes, hydrogen peroxide (H2O2) production, hydrogen break-down activity (HBA) and NO bioavailability. Endothelial function was assessed by brachial flow-mediated dilation (FMD). Platelet function was evaluated by soluble CD40 ligand (sCD40L), soluble P-selectin (sP-selectin) and thrombus formation by T-TAS analysis. Passive smoking-exposed children (both HNBC and TT) exhibited significantly increased serum sNOX2-dp, isoprostanes, H2O2, sCD40L sP-selectin and thrombus formation versus controls. Conversely, exposed children displayed reduced brachial FMD and serum NO bioavailability. No significant differences were found between children exposed to passive smoking of HNBC vs TT. Multivariable regression linked sNOX2 (standardized coefficient β: 0.284; SE: 0.040; p = 0.01) and H2O2 (standardized coefficient β: 0.243; SE: 0.0; p = 0.02) as independent predictors of FMD, and isoprostanes (standardized coefficient β:0.388; SE: 0.022; p < 0.001) and serum cotinine (standardized coefficient β:0.270; SE: 0.048; p = 0.01) with sNOX2-dp levels. Exposure to HNBC smoke heightened oxidative stress, endothelial dysfunction, platelet activation, and thrombus formation in children. Findings suggest avenues for interventions to curb childhood passive smoking exposure.
Magnetic helical microswimmers, called artificial bacterial flagella (ABFs), can perform precise 3D navigation in liquids under low-strength rotating magnetic fields (<10 mT), making themselves promising tools for targeted therapies. On page 1666 S. Fijuta, B. J. Nelson, and team show that the ABFs are functionalized with lipoplexes containing plasmid DNA, and the successful wirelessly targeted gene delivery to human embryonic kidney cells in vitro using these functionalized ABFs is demonstrated.
Platelet activation and oxidative stress seem to play a key role in coronary thrombus formation and are associated with thrombus burden in ST-elevation myocardial infarction (STEMI). However, the interplay between oxidative stress and platelet activation has not been fully elucidated.For 32 patients with STEMI undergoing primary percutaneous coronary intervention (PPCI) and 10 patients with stable angina (SA) and oxidative stress, as assessed by NADPH isoform 2 activity (soluble Nox2-derived peptide, sNox2-dp), levels of oxidized low-density lipoproteins (oxLDLs) and platelet activation markers such as soluble CD40 Ligand (sCD40L) and soluble P-selectin (sP-selectin) were measured in the retrieved material (coronary thrombi plus blood waste) of STEMI patients and in intracoronary blood of SA patients, respectively, and in peripheral blood samples of both groups.In aspirated thrombi and blood waste of STEMI patients we found higher serum levels of sNox2-dp, oxLDLs, sCD40L, and sP-selectin, as compared to the intracoronary blood samples of SA patients. Moreover, in thrombi and blood waste of STEMI patients, a direct correlation between markers of oxidative stress and of platelet activation was found. Also, in STEMI patients a progressive increase of oxidative stress and platelet activation markers was observed according to the thrombus score burden. STEMI patients showed higher peripheral blood Nox2 activity and oxLDL levels as compared to SA patients.This study shows a close relationship between oxidative stress and platelet activation in the intracoronary blood waste and aspirated thrombi of STEMI patients, suggesting a role of oxidative stress in promoting thrombus formation and growth.
The aim of the study was to investigate the in vivo effect of abacavir (ABC) on platelet oxidative stress.We performed a randomized pilot study including 39 HIV-1-infected patients, 17 on zidovudine/lamivudine (ZDV/3TC) and 22 on tenofovir/emtricitabine (TDF/FTC). Ten patients on ZDV/3TC and eight patients on TDF/FTC were randomly allocated to switching the nucleoside backbone to ABC/3TC. At baseline and after 6 months, platelet oxidative stress was assessed by platelet NADPH oxidase 2 (NOX2)-derived peptide (sNOX2-dp), a marker of NOX2 activation, and platelet prostaglandin F2α (8-iso-PGF2α ). Platelet activation was measured by soluble CD40L (sCD40L).At baseline, no differences between ZDV/3TC or TDF/FTC recipients were found. After 6 months, patients switching from ZDV/3TC showed a decrease of sNOX2-dp (from 20.9±5.7 to 12.5±3.8 pg/ml, p=0.002) and 8-iso-PGF2α (from 154.3±41.9 to 122.9±28.0 pmol/l, p=0.025). No effects on platelet oxidative stress biomarkers were observed in subjects from TDF/FTC, who showed a significant increase in blood glucose (p=0.043) and total cholesterol (p=0.027). ABC showed no effect on sCD40L levels in both groups.ABC reduced platelet sNOX2-dp and 8-iso-PGF2α in HIV-1 subjects switching from ZDV/3TC but not in those from TDF/FTC after 6 months. No changes in platelet activation were found in both groups.
Abstract Background High circulating levels of proprotein convertase subtilisin/kexin 9 (PCSK9) were shown to be predictive of cardiovascular events (CVEs) in patients with atrial fibrillation (AF). Because high PCSK9 plasma levels were significantly correlated with 11-dehydro-thromboxane B2 (11-dh-TxB2), a marker of platelet activation, it is conceivable to hypothesize a direct effect of PCSK9 on platelet activation but the mechanism is still unclear. Purpose We evaluated the association between PCSK9 and platelet activation in FA patients and investigate the possible molecular mechanism involved. Methods According to our previous prospective study, we conducted a post-hoc analysis including 50 patients with baseline PCSK9 below and 50 above the median value of 1200pg/ml. The two groups were balanced for age and sex. In vivo platelet activation was assessed by aggregation (PA), recruitment, plasma thromboxane B2 (TxB2) formation and sPselectin levels. As markers of oxidative stress we used sNox2-dp, H2O2 production, urinary isoprostanes and oxLDL. To asses the role of PCSK9 in platelet activation, we performed an in vitro study with platelets from healthy subjects (n=5) added with PCSK9 concentrations achievable in human circulation (1000pg/ml and 2000pg/ml) measuring PA, TxB2, isoprostanes production, Nox2 activation, H2O2 production, oxLDL, p38, p47 and PLA2 phosphorylation. Results We observed an increased of platelet activation and oxidative stress in patients with PCSK9 levels above median (1200pg/ml) compared to those below (p<0.05). A significant correlation between plasma levels of PCSK9 and markers of platelet activation and markers of oxidative stress were found. In vitro study demonstrated that PCSK9, at the concentration similar to that of patients with CVEs, was able to increase platelet activation act by binding oxLDL receptor. PCSK9 dependent platelet activation is mediated by p47 phosphorylation, a key step in Nox2 activation and is mediated by the PLA2 phosporylation. Conclusions PCSK9, at concentration achievable in patients with CVEs, increased platelet aggregation via oxLDL receptor with a pathway involving Nox2 activation.
Objectives: Atrial fibrillation (AF) is characterized by an oxidative imbalance, which is associated with an increased risk of cardiovascular events (CVEs). It is unclear whether low grade endotoxemia may contribute to the impaired antioxidant status in AF patients. We investigated the relationship between circulating lipopolysaccharides (LPS) and antioxidant status in AF patients. Patients and Methods:Post-hoc analysis from the ongoing prospective observational cohort ATHERO-AF study including 907 patients. Antioxidant status was evaluated by the activity of glutathione peroxidase 3 (GPx3) and superoxide dismutase (SOD). Patients were divided into two groups to evaluate the risk of CVEs: (1) LPS below median and GPx3 above median (n = 254); (2) LPS above median and GPx3 below median (n = 263). Results: The mean age was 73.5 ± 8.3 years, and 43.1% were women. Median LPS and GPx3 were 50.0 pg/ml [interquartile range (IQR) 15-108] and 20.0 U/ml (IQR 10.0-34.0), respectively. Patients of Groups 2 were older, with a higher prevalence of heart failure. LPS above the median was associated with reduced GPx3 [Odds Ratio for LPS 1.752, 95% Confidence Interval (CI) 1.344-2.285, p < 0.001] and SOD (OR 0.525, 95%CI 0.403-0.683) activity after adjustment for CHA2DS2VASc score. In a mean follow-up of 54.0 ± 36.8 months, 118 CVEs occurred, 42 in Group 1 and 76 in Group 2 (Log-Rank test p = 0.001). At multivariable Cox regression analysis, Group 2 was associated with a higher risk of CVEs [Hazard Ratio (HR) 1.644, 95%CI 1.117-2,421, p = 0.012], along with age ≥ 75 years (HR 2.035, 95%CI 1.394-2.972, p < 0.001), diabetes (HR 1.927, 95%CI 1.280-2.900, p = 0.002), and previous cerebrovascular disease (HR 1.895, 95%CI 1.251-2.870, p = 0.003) and previous cardiovascular disease (HR 1.708, 95%CI 1.149-2.538, p = 0.008). Conclusions: Our study indicates that circulating LPS may contribute to impaired antioxidant status in patients with AF. Patients with coincidentally high LPS and reduced GPx3 activity showed the highest risk of CVEs.
