Toll-Like Receptor induced CD11b and L-selectin response in patients with coronary artery disease

Toll-Like Receptor (TLR) -2 and -4 expression and TLR-induced cytokine response of inflammatory cells are related to atherogenesis and atherosclerotic plaque progression. We examined whether immediate TLR induced changes in CD11b and L-selectin (CD62L) expression are able to discriminate the presence and severity of atherosclerotic disease by exploring single dose whole blood TLR stimulation and detailed dose-response curves. Blood samples were obtained from 125 coronary artery disease (CAD) patients and 28 controls. CD11b and L-selectin expression on CD14+ monocytes was measured after whole blood stimulation with multiple concentrations of the TLR4 ligand LPS (0.01-10 ng/ml) and the TLR2 ligand P3C (0.5-500 ng/ml). Subsequently, dose-response curves were created and the following parameters were calculated: hillslope, EC50, area under the curve (AUC) and delta. These parameters provide information about the maximum response following activation, as well as the minimum trigger required to induce activation and the intensity of the response. CAD patients showed a significantly higher L-selectin, but not CD11b response to TLR ligation than controls after single dose stimulations as well as significant differences in the hillslope and EC50 of the dose-response curves. Within the CAD patient group, dose-response curves of L-selectin showed significant differences in the presence of hypertension, dyslipidemia, coronary occlusion and degree of stenosis, whereas CD11b expression had the strongest discriminating power after single dose stimulation. In conclusion, single dose stimulations and dose-response curves of CD11b and L-selectin expression after TLR stimulation provide diverse but limited information about atherosclerotic disease severity in stable angina patients. However, both single dose stimulation and dose-response curves of LPS-induced L-selectin expression can discriminate between controls and CAD patients.Biopharmaceutic

Ebstein's anomaly may be caused by mutations in the sarcomere protein gene MYH7

Ebstein's anomaly is a rare congenital heart malformation characterised by adherence of the septal and posterior leaflets of the tricuspid valve to the underlying myocardium. Associated abnormalities of left ventricular morphology and function including left ventricular noncompaction (LVNC) have been observed. An association between Ebstein's anomaly with LVNC and mutations in the sarcomeric protein gene MYH7, encoding β -myosin heavy chain, has been shown by recent studies. This might represent a specific subtype of Ebstein's anomaly with a Mendelian inheritance pattern. In this review we discuss the association of MYH7 mutations with Ebstein's anomaly and LVNC and its implications for the clinical care for patients and their family members

Gastrointestinal symptoms in diabetes mellitus, and their relation to anxiety and depression

BACKGROUND: Prevalence of gastrointestinal (GI) symptoms is increased in patients with diabetes mellitus. In general, GI symptoms are influenced by psychological factors such as anxiety and depression, but little is known about this association in diabetic patients. AIM: We tested the hypothesis that anxiety and depression have major impact on GI symptoms in diabetic patients. METHODS: 280 diabetic patients and 355 non-diabetic, age and sex matched controls were studied by validated questionnaires: (1) PAGI-SYM and GSRS for common GI symptoms and (2) HADS for anxiety and depression. Data were compared using logistic regression analysis. RESULTS: Patients with diabetes scored significantly (p/=8) in diabetics and controls was respectively 27.5% and 20.6% for anxiety (p<0.05), and 19.6% and 13.4% for depression (p<0.05). After adjusting for anxiety and depression only the GI symptom "early satiety" remained significantly more prevalent in the patients with diabetes. CONCLUSIONS: The prevalence of the gastrointestinal symptoms diarrhea, bloating and early satiety, and of anxiety and depression is significantly increased in our cohort of predominantly patients with longstanding type 2 diabetes mellitus compared to controls. When adjusted for anxiety and depression, only the gastrointestinal symptom "early satiety" remained more prevalent in these diabetic patients, pointing to a somatic based origin. Thus, in our diabetic population psychological factors to a large extent are associated with gastrointestinal symptoms and should be taken into account when considering treatment of the gastrointestinal symptoms

Fractional flow reserve is not associated with inflammatory markers in patients with stable coronary artery disease

AbstractBACKGROUND: Atherosclerosis is an inflammatory condition and increased blood levels of inflammatory biomarkers have been observed in acute coronary syndromes. In addition, high expression of inflammatory markers is associated with worse prognosis of coronary artery disease. The presence and extent of inducible ischemia in patients with stable angina has previously been shown to have strong prognostic value. We hypothesized that evidence of inducible myocardial ischemia by local lesions, as measured by fractional flow reserve (FFR), is associated with increased levels of blood based inflammatory biomarkers.METHODS: Whole blood samples of 89 patients with stable angina pectoris and 16 healthy controls were analyzed. The patients with stable angina pectoris underwent coronary angiography and FFR of all coronary lesions. We analyzed plasma levels of cytokines IL-6, IL-8 and TNF-α and membrane expression of Toll-like receptor 2 and 4, CD11b, CD62L and CD14 on monocytes and granulocytes as markers of inflammation. Furthermore, we quantified the severity of hemodynamically significant coronary artery disease by calculating Functional Syntax Score (FSS), an extension of the Syntax Score.RESULTS: For the majority of biomarkers, we observed lower levels in the healthy control group compared with patients with stable angina who underwent coronary catheterization. We found no difference for any of the selected biomarkers between patients with a positive FFR (≤ 0.75) and negative FFR (>0.80). We observed no relationship between the investigated biomarkers and FSS.CONCLUSION: The presence of local atherosclerotic lesions that result in inducible myocardial ischemia as measured by FFR in patients with stable coronary artery disease is not associated with increased plasma levels of IL-6, IL-8 and TNF-α or increased expression of TLR2 and TLR4, CD11b, CD62L and CD14 on circulating leukocytes.Biopharmaceutic

Meta-Analysis Evaluating High-Sensitivity Cardiac Troponin T Kinetics after Coronary Artery Bypass Grafting in Relation to the Current Definitions of Myocardial Infarction

Various definitions of myocardial infarction type 5 after coronary artery bypass grafting (CABG) have been proposed (myocardial infarction [MI-5], also known as peri-procedural MI), using different biomarkers and different and arbitrary cut-off values. This meta-analysis aims to determine the expected release of high-sensitivity cardiac troponin T (hs-cTnT) after CABG in general and after uncomplicated surgery and off-pump CABG in particular. A systematic search was applied to 3 databases. Studies on CABG as a single intervention and reporting on postoperative hs-cTnT concentrations on at least 2 different time points were included. All data on hs-cTnT concentrations were extracted, and mean concentrations at various points in time were stratified. Eventually, 15 studies were included, encompassing 2,646 patients. Preoperative hs-cTnT was 17 ng/L (95% confidence interval [CI] 13 to 20 ng/L). Hs-cTnT peaked at 6 to 8 hours postoperatively (628 ng/L, 95% CI 400 to 856 ng/L; 45x upper reference limit [URL]) and was still increased after 48 hours. In addition, peak hs-cTnT concentration was 614 ng/L (95% CI 282 to 947 ng/L) in patients with a definite uncomplicated postoperative course (i.e., without MI). For patients after off-pump CABG compared to on-pump CABG, the mean peak hs-cTnT concentration was 186 ng/L (95% CI 172 to 200 ng/L, 13 x URL) versus 629 ng/L (95% CI 529 to 726 ng/L, 45 x URL), respectively. In conclusion, postoperative hs-cTnT concentrations surpass most of the currently defined cut-off values for MI-5, even in perceived uncomplicated surgery, suggesting thorough reassessment. Hs-cTnT release differences following on-pump CABG versus off-pump CABG were observed, implying the need for different cut-off values for different surgical strategies. (C) 2021 The Author(s). Published by Elsevier Inc

Increased cytokine response after toll-like receptor stimulation in patients with stable coronary artery disease

Nephrolog

Identifying Sn site heterogeneities prevalent among Sn-Beta zeolites

In recent years, various protocols on preparing Lewis acidic Sn-β zeolite hydrothermally and post-synthetically have been reported. However, very little is known about the effects of different synthesis protocols on the SnIV speciation in the final material. Even the effects of individual synthesis parameters within a certain preparation method have not been studied systematically. Here, we demonstrate that hydrothermally synthesized Sn-β zeolites prepared via very similar recipes show significantly different 119Sn NMR spectra, suggesting different Sn site speciation. Among post-synthetically prepared Sn-β zeolites, less variation in the resulting 119Sn NMR spectra have been observed, indicating a more reproducible synthesis procedure compared to hydrothermal synthesis in fluoride media. This work highlights the importance of 119Sn NMR measurements to elucidate the precise local geometry of the Sn heteroatoms in Sn-β, and the need to quantify the number of reactive Sn sites on each sample that participate in a given catalytic reaction, in order to accurately compare materials prepared by different routes

Monocyte gene expression in childhood obesity is associated with obesity and complexity of atherosclerosis in adults

Childhood obesity coincides with increased numbers of circulating classical CD14++CD16- and intermediate CD14++CD16+ monocytes. Monocytes are key players in the development and exacerbation of atherosclerosis, which prompts the question as to whether the monocytosis in childhood obesity contributes to atherogenesis over the years. Here, we dissected the monocyte gene expression profile in childhood obesity using an Illumina microarray platform on sorted monocytes of 35 obese children and 16 lean controls. Obese children displayed a distinctive monocyte gene expression profile compared to lean controls. Upon validation with quantitative PCR, we studied the association of the top 5 differentially regulated monocyte genes in childhood obesity with obesity and complexity of coronary atherosclerosis (SYNTAX score) in a cohort of 351 adults at risk for ischemic cardiovascular disease. The downregulation of monocyte IMPDH2 and TMEM134 in childhood obesity was also observed in obese adults. Moreover, downregulation of monocyte TMEM134 was associated with a higher SYNTAX atherosclerosis score in adults. In conclusion, childhood obesity entails monocyte gene expression alterations associated with obesity and enhanced complexity of coronary atherosclerosis in adults