IL-33 promotes IL-10 production in macrophages: a role for IL-33 in macrophage foam cell formation

We evaluated the role of IL-10- in IL-33-mediated cholesterol reduction in macrophage-derived foam cells (MFCs) and the mechanism by which IL-33 upregulates IL-10. Serum IL-33 and IL-10 levels in coronary artery disease patients were measured. The effects of IL-33 on intra-MFC cholesterol level, IL-10, ABCA1 and CD36 expression, ERK 1/2, Sp1, STAT3 and STAT4 activation, and IL-10 promoter activity were determined. Core sequences were identified using bioinformatic analysis and site-specific mutagenesis. The serum IL-33 levels positively correlated with those of IL-10. IL-33 decreased cellular cholesterol level and upregulated IL-10 and ABCA1 but had no effect on CD36 expression. siRNA-IL-10 partially abolished cellular cholesterol reduction and ABCA1 elevation by IL-33 but did not reverse the decreased CD36 levels. IL-33 increased IL-10 mRNA production but had little effect on its stability. IL-33 induced ERK 1/2 phosphorylation and increased the luciferase expression driven by the IL-10 promoter, with the highest extent within the −2000 to −1752 bp segment of the 5′-flank of the transcription start site; these effects were counteracted by U0126. IL-33 activated Sp1, STAT3 and STAT4, but only the STAT3 binding site was predicted in the above segment. Site-directed mutagenesis of the predicted STAT3-binding sites (CTGCTTCCTGGCAGCAGAA→CTGCCTGGCAGCAGAA) reduced luciferase activity, and a STAT3 inhibitor blocked the regulatory effects of IL-33 on IL-10 expression. Chromatin immunoprecipitation (CHIP) confirmed the STAT3-binding sequences within the −1997 to −1700 and −1091 to −811 bp locus regions. IL-33 increased IL-10 expression in MFCs via activating ERK 1/2 and STAT3, which subsequently promoted IL-10 transcription and thus contributed to the beneficial effects of IL-33 on MFCs.

Biomarkers of endothelial dysfunction and risk of early organ damage: a comparison between patients with primary aldosteronism and essential hypertension / 中华心血管病杂志

<p><b>OBJECTIVE</b>To compare plasma concentrations of biomarkers of endothelial dysfunction between patients with primary aldosteronism (PA) and essential hypertension (EH), and to determine whether elevated levels of these biomarkers could predict development of early organ damage.</p><p><b>METHODS</b>Thirty-six PA patients and 39 EH patients matched for age, sex, blood pressure and duration of hypertension were included in this study. Plasma levels of biomarkers reflecting endothelial dysfunction (von Willebrand factor, vWF; soluble intercellular adhesion molecule 1, sICAM-1; and oxidized low density lipoprotein, ox-LDL) were detected and compared between PA and EH patients. Left ventricular mass index (LVMI) determined by echocardiography, 24-hour urinary protein quantitative determination and urinary albumin excretion rate (UAER) were analyzed to evaluate early organ damage. Left ventricular hypertrophy was defined as LVMI > 125 g/m(2) in men and > 120 g/m(2) in women, and UAER between 20 µg/min and 200 µg/min was defined as microalbuminuria.</p><p><b>RESULTS</b>vWF [(122.3 ± 53.8)% vs. (113.1 ± 68.3)%], sICAM-1 [(401.0 ± 74.1) µg/L vs. (300.9 ± 87.0) µg/L], ox-LDL [(13.6 ± 10.0) U/L vs. (8.1 ± 5.9) U/L], LVMI [(124.7 ± 33.6) g/m(2) vs. (109.1 ± 25.7) g/m(2)], 24-hour urinary protein quantitation [24 h UPQ, (0.17 ± 0.10) g vs. (0.09 ± 0.04) g] and UAER [(25.9 ± 7.7) µg/min vs. (9.7 ± 5.9) µg/min] were significantly higher in PA group than in EH group (all P < 0.05). Elevated plasma vWF, sICAM-1 levels and plasma aldosterone concentration independently predicted microalbuminuria. Whereas, elevated plasma vWF and ox-LDL levels, plasma aldosterone concentration and systolic blood pressure independently predicted left ventricular hypertrophy.</p><p><b>CONCLUSION</b>Patients with PA have severer endothelial dysfunction reflected by multiple biomarkers and earlier organ damage than patients with EH, and plasma aldosterone concentration and multiple endothelial dysfunction biomarkers could independently predict early organ damage.</p>

Diagnostic value of 64-slice spiral computed tomography coronary angiography for coronary artery disease / 中华心血管病杂志

<p><b>OBJECTIVE</b>To assess the diagnostic accuracy of 64-slice computed tomography coronary angiography (64-SCTCA) in individuals with suspected coronary artery disease (CAD).</p><p><b>METHODS</b>The study enrolled 285 individuals undergoing 64-SCTCA with calcium scoring and thereafter invasive coronary angiography (CAG) within 4 weeks for suspected CAD. Pretest probability of having obstructive CAD was determined using the Duke clinical score, which was estimated by type of chest discomfort, age, gender, and traditional risk factors and stratified into 3 levels of probability: low (≤ 30%, n = 80), intermediate (31% to 70%, n = 92), and high (≥ 71%, n = 113). CAD was defined as the presence of at least one vessel of ≥ 50% coronary stenosis on CAG.</p><p><b>RESULTS</b>The patient-based diagnostic accuracy of 64-SCTCA for detecting CAD according to CAG revealed a sensitivity of 81.2%, a specificity of 93.3%, a positive predictive value of 68.0% and negative predictive value of 96.6%. The CAD prevalence in the low, intermediate and high risk groups according to Duke probability was 46.3%, 72.8% and 82.3%, respectively. The sensitivity and positive predictive value were lower in the low probability group than those in the intermediate and high probability groups. For those with coronary artery Agatston calcium score > 400, the diagnostic accuracy was linked with a higher sensitivity but lower specificity. The diagnostic value of 64-SCTCA for proximal and mid-segment of coronary artery was superior to that for distal segment.</p><p><b>CONCLUSIONS</b>64-SCTCA is mainly indicated in individuals with an intermediate probability of having CAD. The diagnostic value of 64-SCTCA could be affected by coronary artery calcium, lesion location and vessel diameter.</p>

Impact of mean fasting glucose over the first 72 hours on in-hospital outcomes of patients with ST-segment elevation myocardial infarction / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the impact of mean fasting glucose over the first 72 hours after admission on in-hospital outcomes in patients with ST-segment elevation myocardial infarction (STEMI).</p><p><b>METHODS</b>The data of 357 non-diabetic patients hospitalized with STEMI were collected from the database of Sun Yat-sen Memorial Hospital, affiliated to Sun Yat-sen University between January 2006 and April 2009. The patients were categorized into 3 groups according to mean fasting glucose over the first 72 hours after admission: < 5.6 (n = 165), 5.6 - 7.0 (n = 122) and > 7.0 mmol/L (n = 70). Clinical characteristics, therapeutic approaches and the incidence of heart failure, malignant arrhythmias, and death during hospitalization were compared among groups. Multivariate logistic regression analysis was performed to determine the association between risk factors and in-hospital outcomes. Receiver-operator characteristic (ROC) curve was generated to assess the power of mean fasting glucose on predicting in-hospital death.</p><p><b>RESULTS</b>Age, past history of infarction and early revascularization therapy were similar among groups. Heart rate on admission, white blood cell count, peak CK-MB level, and proportion of extensive anterior infarction were increased in proportion to higher mean fasting glucose levels. Higher mean fasting glucose levels were associated with increased risk of reduced left ventricular ejection fraction, heart failure characterized by higher Killip class, and malignant arrhythmias. After multivariate adjustment, mean fasting glucose remained to be an independent risk factor for increased in-hospital death of patients with STEMI (OR = 1.31, 95%CI: 1.10 - 1.57; P = 0.003). Mean fasting glucose had the higher area under the ROC curve than admission glucose or fasting glucose after admission based on single measurement (0.758, 0.674 and 0.717; P < 0.001).</p><p><b>CONCLUSION</b>Mean fasting glucose during first 72 hours after admission is an independent predictor for in-hospital death and complications in patients with STEMI, which is superior to admission glucose or fasting glucose after admission based on single measurement in predicting in-hospital outcomes.</p>

Alcohol consumption and coronary heart disease in Eastern Asian men: a meta-analysis of prospective cohort studies / 中华心血管病杂志

<p><b>OBJECTIVE</b>To assess the dose-response relationship between alcohol consumption and relative risk of coronary heart disease (CHD) morbidity, mortality and all-cause mortality among Eastern Asian men.</p><p><b>METHODS</b>Potential prospective cohort studies were retrieved by searching Pubmed (1966 - 2000), Biosis Previews (1980 - 2009), Embase (1980 - 2009) and ISI Web of Knowledge (1986 - 2009) using Medical Subject Headings alcohol drinking, ethanol, coronary heart (or artery) disease, myocardial infarction, mortality, etc; and Koreans, or Japanese or Chinese. From the 28 relevant retrieved reports, 15 prospective cohort studies met the criteria were included. Information on study design, participant characteristics, level of alcohol consumption, CHD outcome, control for potential confounding factors, and risk estimates were abstracted using a standardized protocol. For each study, relative risks (RR) and 95% confidence intervals (CI) were extracted and pooled with either a fixed effect model or random effect model according to the result of the test of heterogeneity.</p><p><b>RESULTS</b>Due to the limited available data for women, this study only comprised of 2406 cases of CHD among 177 723 male subjects. Findings were also pooled from 216 233 male subjects and 15 462 deaths from any cause. Compared with nondrinkers, the RRs on CHD morbidity for those who drank alcohol ≤ 20, 21 - 40, 41 - 60, > 60 g/d were 0.65 (0.34 - 1.23, P = 0.18), 0.48 (0.26 - 0.87, P = 0.02), 0.46 (0.32 - 0.67, P < 0.01), and 0.48 (0.29 - 0.78, P < 0.01) respectively; the RRs on CHD mortality were 0.98 (0.73 - 1.31, P = 0.87), 0.68 (0.58 - 0.79, P < 0.01), 0.64 (0.43 - 0.96, P = 0.03), 0.75 (0.54 - 1.03, P = 0.08); and on all-cause mortality were 0.83 (0.79 - 0.91, P < 0.01), 0.93 (0.87 - 0.99, P = 0.03), 1.01 (0.95 - 1.07, P = 0.86), 1.32 (1.29 - 1.36, P < 0.01).</p><p><b>CONCLUSION</b>Light-to-moderate alcohol intake was associated with decreased risk of CHD morbidity and mortality, while heavy alcohol intake was associated with increased all-cause mortality among Eastern Asian men.</p>

R25G mutation in exon 1 of LMNA gene is associated with dilated cardiomyopathy and limb-girdle muscular dystrophy 1B / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Mutations of the LMNA gene encoding lamin A and C are associated with dilated cardiomyopathy (DCM), conduction system defects and skeletal muscle dystrophy. Here we report a family with a mutation of the LMNA gene to identify the relationship between genotype and phenotype.</p><p><b>METHODS</b>All 30 members of the family underwent clinical and genetic evaluation. A mutation analysis of the LMNA gene was performed. All of the 12 exons of LMNA gene were extended with polymerase chain reaction (PCR) and the PCR products were screened for gene mutation by direct sequencing.</p><p><b>RESULTS</b>Ten members of the family had limb-girdle muscular dystrophy (LGMD) and 6 are still alive. Two patients suffered from DCM. Cardiac arrhythmias included atrioventricular block and atrial fibrillation; sudden death occurred in 2 patients. The pattern of inheritance was autosomal dominant. Mutation c.73C > G (R25G) in exon 1 encoding the globular domains was confirmed in all of the affected members, resulting in the conversion of arginine (Arg) to glycine (Gly).</p><p><b>CONCLUSIONS</b>The mutation R25G in exon 1 of LMNA gene we reported here in a Chinese family had a phenotype of malignant arrhythmia and mild LGMD, suggesting that patients with familial DCM, conduction system defects and skeletal muscle dystrophy should be screened by genetic testing for the LMNA gene.</p>

Comparison of clinical course of patients with severe acute respiratory syndrome among the multiple generations of nosocomial transmission / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Severe acute respiratory syndrome (SARS) is characterized by both an atypical pneumonia and efficient nosocomial transmission. However, it remains unknown whether the infectivity and the virulence of the pathogen will change throughout the successive transmission. This study was conducted to compare the clinical features and management regimens of patients with SARS among the multiple generations from nosocomial transmission initiated by a super-spreader.</p><p><b>METHODS</b>The clinical data of 84 epidemiologically-linked SARS patients from a hospital outbreak were retrospectively studied. All patients, in whom a clear-cut transmission generation could be noted, had a direct or indirect exposure to the index patient and the epidemic successively propagated through the multiple generations of cases within a short period of time.</p><p><b>RESULTS</b>There were 66 women and 18 men with mean age of (29.2 +/- 10.3) years in this cluster; and 96.4% of whom were health care workers. Detailed contact tracing identified 35 (41.7%) first-generation cases, 34 (40.5%) second-generation cases, and 15 (17.8%) third-generation cases. No statistical differences among the multiple generations of transmission were found in terms of age, gender, incubation period and length of hospital stay. With the advanced transmission generations, the initial temperature lowered, the number of cases with dry cough decreased. There were no statistical differences in the peak temperature and duration of fever, other accompanying symptoms, leucopenia; however, the time from initial pulmonary infiltrates to radiographic recovery shortened (P < 0.05). No differences were found in maximum number of lung fields involved, duration from the onset of fever to the occurrence of pulmonary infiltrates and time from the initial pulmonary infiltrate to its peak among the multiple transmission generations (P > 0.05). No statistical differences were found in modes of oxygen therapy and sorts of antibiotics prescribed among the various transmission generations (P > 0.05); however, as with the advanced transmission generations, the number of cases prescribed with methylprednisolone, human gamma-globulin, interferon-alpha, antiviral drugs (oral ribavirin or oseltamivir) increased (P < 0.05) and time from admission to starting these medication shortened (P < 0.05).</p><p><b>CONCLUSIONS</b>There is no evidence that SARS infection will evolve or transmit within a fashion that permits it to become less powerful throughout the successive transmission within a short time.</p>