Low-grade endotoxemia and NOX2 in patients with coronary microvascular angina.

BACKGROUND: Endothelial dysfunction and oxidative stress were hypothesized to be involved in the pathogenesis of coronary microvascular angina (MVA). NADPH oxidase-2 (NOX2) activation could provoke increased oxidative stress and endothelial dysfunction, but data on MVA have not been provided yet. AIMS: This study aimed to evaluate the interaction among NOX2 activation, serum lipopolysaccharide (LPS) levels, as well as oxidative stress production as potential causes of endothelial dysfunction in MVA patients. METHODS: In this study, we wanted to compare serum levels of soluble NOX2-dp (sNOX2-dp), H2O2 production, hydrogen peroxide breakdown activity (HBA), nitric oxide (NO) bioavailability, endothelin 1 (ET-1), serum zonulin (as intestinal permeability assay), and LPS in 80 consecutive subjects, including 40 MVA patients and 40 controls (CT), matched for age and sex. RESULTS: Compared with CT, MVA patients had significantly higher values of sNOX2-dp, H2O2, ET-1, LPS, and zonulin. Conversely HBA and NO bioavailability were significantly lower in MVA patients. Simple linear regression analysis showed that sNOX2 was associated with serum LPS, serum zonulin, H2O2, and ET-1. Furthermore, an inverse correlation between sNOX2, HBA, and nitric oxide bioavailability was observed. Multiple linear regression analysis showed that LPS and zonulin emerged as the only independent predictive variables associated with sNOX2. CONCLUSIONS: This study provides the first report attesting that patients with MVA have high LPS levels, NOX2 activation, and an imbalance between pro-oxidant and antioxidant systems, in favor of the oxidizing molecules that could be potentially implicated in the endothelial dysfunction and vasoconstriction of this disease.

Is There an Association Between Atherosclerotic Burden, Oxidative Stress, and Gut-Derived Lipopolysaccharides?

Aims: Recent studies hypothesized a role of gut microbiota favoring atherosclerosis via an increased oxidative stress, but data in peripheral artery disease (PAD) have not been provided yet. The aim of this study was to assess serum lipopolysaccharide (LPS) as well as oxidative stress in PAD patients and controls (CT). Furthermore, we wanted to analyze the relationship between LPS and the severity of atherosclerosis in the lower limb arteries. Results: Eighty consecutive subjects, including 40 PAD patients and 40 CT were recruited. A cross-sectional study was performed to compare serum LPS, soluble Nox2-derived peptide (sNox2-dp), hydrogen peroxide (H2O2), H2O2 breakdown activity (HBA) and ankle brachial index (ABI) in these two groups. Serum zonulin was used to assess gut permeability. Compared with CT, PAD patients had significant higher values of LPS, zonulin, sNox2-dp, and H2O2; conversely ABI and HBA were significantly lower in PAD patients. LPS serum levels were associated with atherosclerotic burden as depicted by the inverse correlation with ABI. LPS was also associated with oxidative stress as shown by its direct correlation with markers of oxidative stress such as sNox2-dp, serum H2O2, and HBA. Finally, we found a significant correlation between LPS and zonulin. A multiple linear regression analysis showed that LPS was significantly associated only with ABI. Innovation and Conclusion: These findings suggest that LPS is elevated in PAD patients with a close association with the atherosclerotic burden and oxidative stress. The correlation between LPS and zonulin suggests that changes in gut permeability could be a potential trigger of LPS translocation in the peripheral circulation.

Patients with rheumatoid arthritis facing sick leave or work disability meet varying regulations: a study among rheumatologists and patients from 44 European countries.

OBJECTIVES: To describe and explore differences in formal regulations around sick leave and work disability (WD) for patients with rheumatoid arthritis (RA), as well as perceptions by rheumatologists and patients on the system's performance, across European countries. METHODS: We conducted three cross-sectional surveys in 50 European countries: one on work (re-)integration and social security (SS) system arrangements in case of sick leave and long-term WD due to RA (one rheumatologist per country), and two among approximately 15 rheumatologists and 15 patients per country on perceptions regarding SS arrangements on work participation. Differences in regulations and perceptions were compared across categories defined by gross domestic product (GDP), type of social welfare regime, European Union (EU) membership and country RA WD rates. RESULTS: Forty-four (88%) countries provided data on regulations, 33 (75%) on perceptions of rheumatologists (n=539) and 34 (77%) on perceptions of patients (n=719). While large variation was observed across all regulations across countries, no relationship was found between most of regulations or income compensation and GDP, type of SS system or rates of WD. Regarding perceptions, rheumatologists in high GDP and EU-member countries felt less confident in their role in the decision process towards WD (ß=-0.5 (95% CI -0.9 to -0.2) and ß=-0.5 (95% CI -1.0 to -0.1), respectively). The Scandinavian and Bismarckian system scored best on patients' and rheumatologists' perceptions of regulations and system performance. CONCLUSIONS: There is large heterogeneity in rules and regulations of SS systems across Europe in relation to WD of patients with RA, and it cannot be explained by existing welfare regimes, EU membership or country's wealth.