HEG1 Protects Against Atherosclerosis by Regulating Stable Flow-Induced KLF2/4 Expression in Endothelial Cells.

BACKGROUND: Atherosclerosis preferentially occurs in arterial regions of disturbed blood flow, and stable flow (s-flow) protects against atherosclerosis by incompletely understood mechanisms. METHODS: Our single-cell RNA-sequencing data using the mouse partial carotid ligation model was reanalyzed, which identified Heart-of-glass 1 (HEG1) as an s-flow-induced gene. HEG1 expression was studied by immunostaining, quantitive polymerase chain reaction, hybridization chain reaction, and Western blot in mouse arteries, human aortic endothelial cells (HAECs), and human coronary arteries. A small interfering RNA-mediated knockdown of HEG1 was used to study its function and signaling mechanisms in HAECs under various flow conditions using a cone-and-plate shear device. We generated endothelial-targeted, tamoxifen-inducible HEG1 knockout (HEG1iECKO) mice. To determine the role of HEG1 in atherosclerosis, HEG1iECKO and littermate-control mice were injected with an adeno-associated virus-PCSK9 [proprotein convertase subtilisin/kexin type 9] and fed a Western diet to induce hypercholesterolemia either for 2 weeks with partial carotid ligation or 2 months without the surgery. RESULTS: S-flow induced HEG1 expression at the mRNA and protein levels in vivo and in vitro. S-flow stimulated HEG1 protein translocation to the downstream side of HAECs and release into the media, followed by increased messenger RNA and protein expression. HEG1 knockdown prevented s-flow-induced endothelial responses, including monocyte adhesion, permeability, and migration. Mechanistically, HEG1 knockdown prevented s-flow-induced KLF2/4 (Kruppel-like factor 2/4) expression by regulating its intracellular binding partner KRIT1 (Krev interaction trapped protein 1) and the MEKK3-MEK5-ERK5-MEF2 pathway in HAECs. Compared with littermate controls, HEG1iECKO mice exposed to hypercholesterolemia for 2 weeks and partial carotid ligation developed advanced atherosclerotic plaques, featuring increased necrotic core area, thin-capped fibroatheroma, inflammation, and intraplaque hemorrhage. In a conventional Western diet model for 2 months, HEG1iECKO mice also showed an exacerbated atherosclerosis development in the arterial tree in both sexes and the aortic sinus in males but not in females. Moreover, endothelial HEG1 expression was reduced in human coronary arteries with advanced atherosclerotic plaques. CONCLUSIONS: Our findings indicate that HEG1 is a novel mediator of atheroprotective endothelial responses to flow and a potential therapeutic target.

Coffee consumption and abdominal aortic calcification among adults with and without hypertension, diabetes, and cardiovascular diseases.

BACKGROUND AND AIMS: This study was performed to investigate the effect of coffee consumption on abdominal aortic calcification (AAC) among adults with and without hypertension, diabetes, and cardiovascular diseases (CVD). METHODS AND RESULTS: A total of 2548 participants from the National Health and Nutrition Examination Survey (NHANES) 2013-2014 were included. Coffee consumption was obtained from 24-h dietary recalls. Dual-energy X-ray absorptiometry (DXA) was used to measure the severity of AAC. In the fully adjusted model, compared with non-drinkers, high coffee consumption (≥390 g/d) was associated with higher AAC scores among participants with hypertension (ß = 0.72, 95% CI: 0.21-1.22), diabetes (ß = 1.20, 95% CI: 0.35-2.05), and CVD (ß = 2.03, 95% CI: 0.71-3.36). We did not observe such an association among participants without hypertension, diabetes, and CVD. Furthermore, decaffeinated coffee was not associated with AAC. CONCLUSION: In conclusion, patients with hypertension, diabetes, and CVD should focus on coffee consumption, especially caffeinated coffee, to reduce the burden of AAC.

Moderate selenium alleviates the pulmonary function impairment induced by cadmium and lead in adults: A population-based study.

Selenium (Se) has been reported to have an antagonistic effect on heavy metals in animals. However, there is no epidemiological study investigating whether Se could protect against the pulmonary toxicity of Cadmium (Cd) and Lead (Pb). Data was collected from the 2011-2012 National Health and Nutrition Examination Survey (NHANES) cycle. Pulmonary function was assessed by Forced Vital Capacity (FVC), Forced Expiratory Volume 1st Second (FEV1) and FEV1/FVC. Blood concentrations of Cd, Pb, and Se were measured using inductively coupled plasma mass spectrometry. Linear regression, restricted cubic splines, and quantile-based g-computation (qgcomp) were performed to evaluate the individual and joint associations of Cd and Pb with pulmonary function and whether Se modified these associations. In the adjusted multi-metal model, every 1-unit increase in Cd, FEV1, FVC, and FEV1/FVC decreased by 76.437 mL (95 % CI: -110.928 to -41.947), 42.719 mL (95 % CI: -84.553 to -0.885), and 0.012 (95 % CI: -0.016 to -0.007), respectively. Meanwhile, FEV1 decreased by 9.37 mL (95 % CI: -18.61 to -0.13) for every 1 unit increase in Pb. Furthermore, we found an inverted U-shape association between Se and lung function, and participants in the second quartile Se group had the highest increases in FEV1 and FVC compared with participants in the lowest quartile. Qgcomp model also revealed that the toxic metal mixture (Cd and Pb) exhibited a significant inverse association with FEV1 and FEV1/FVC. Furthermore, we found that the inverse association of Pb and Cd, either alone or in combination, with pulmonary function first diminished with increasing Se levels but was re-enforced when blood Se concentrations were in the highest quartile. Our results indicated that moderate Se attenuated the harmful effects of Cd and Pb on lung function.

Lung function indices do not affect the incidence of coronary heart disease in patients with sleep-disordered breathing.

BACKGROUND: Currently, it's unclear whether sleep-disordered breathing (SDB) and reduced lung function could synergistically increase the incidence of coronary heart disease (CHD). Furthermore, the predictive value of different lung function indices for the incidence of CHD remains unknown. METHODS: We enrolled 3749 participants from the Sleep Heart Health Study (SHHS) to conduct a retrospective study. The individuals were divided into the SDB and non-SDB subgroups according to Apnoea-Hypopnoea Index (AHI). Cox regression models were used to evaluate the association between lung function and CHD. We also conducted a ROC analysis to assess the predictive value of different lung function indices. RESULTS: 512 cases of CHD were identified during an average of 10.40 years of follow-up in participants without CVD at baseline. We observed that lung function was a better predictor of CHD in non-SDB participants compared with SDB participants. Reduced lung function was associated with a higher risk of CHD in participants without SDB, while the inverse association became non-significant in participants with SDB. Furthermore, the incremental contribution of lung function to CHD diminished with increasing severity of SDB. CONCLUSION: We need to focus more on the lung function of individuals without SDB rather than those with SDB to reduce the risk of CHD.

Relation of Red Cell Distribution Width to Glucose Metabolism and Adverse Long-Term Prognosis in Patients with Acute Coronary Syndrome.

Introduction: Red cell distribution width (RDW) reflects the heterogeneity of red blood cell size. However, few studies examined whether RDW is related to glucose metabolism indices, such as fasting blood glucose (FBG) and hemoglobin A1c (HbA1c), diabetic mellitus (DM) state or long-term outcomes of acute coronary syndrome (ACS) patients. Methods and Results: A total of 448 consecutive patients with ACS were enrolled in this study. All patients were followed up for major cardiovascular adverse events (MACEs), and the mean follow-up was 952 days. Linear regression analysis showed that RDW inversely correlated with FBG but not HbA1c or DM. Kaplan-Meier survival curve analysis demonstrated that higher RDW levels were significantly positively associated with MACEs in the whole study population and the ACS patients with high FBG but not the low FBG group. Cox multivariate regression analysis revealed the independent function of RDW on MACEs in all ACS patients and ACS patients with high FBG. The receiver operating characteristic (ROC) curve demonstrated the optimal cutoff value of RDW for MACEs. Conclusion: We first reported that higher RDW was associated with decreased FBG but not HbA1c or DM and an increased risk of MACEs in patients with ACS. This relationship was also found in ACS patients with higher FBG levels but not in ACS patients with lower FBG.

Ideal Cardiovascular Health Metrics Are Associated with Reduced Severity of Hepatic Steatosis and Liver Fibrosis Detected by Transient Elastography.

Life's Simple 7 (LS7) is the American Heart Association's (AHA) proposal for a healthy lifestyle, also known as cardiovascular health (CVH) metrics. However, the association between CVH metrics and the severity of hepatic steatosis and liver fibrosis detected by transient elastography is unknown. We performed a cross-sectional study using the data from the 2017-2018 National Health and Nutrition Examination Survey (NHANES) cycle. The controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) were used to evaluate the severity of hepatic steatosis and liver fibrosis and to define NAFLD, advanced liver fibrosis, and cirrhosis. A total of 2679 participants were included. Multivariate linear regression analysis revealed that per 1-unit increase in the CVH metric, CAP and LSM decreased by 8.565 units and 0.274 units, respectively. In the multivariate logistic regression analysis, the risk of NAFLD, advanced liver fibrosis, and cirrhosis were 7, 10, and 6 times higher in the poor CVH group than in the ideal CVH group. Subgroup analysis indicated that CVD patients and non-Hispanic whites could benefit more from ideal CVH. In conclusion, adherence to ideal CVH metrics, as proposed by the AHA, can significantly reduce the risk of hepatic steatosis and liver fibrosis.

Relationship between Red Blood Cell Indices (MCV, MCH, and MCHC) and Major Adverse Cardiovascular Events in Anemic and Nonanemic Patients with Acute Coronary Syndrome.

Background: Previous studies have shown that increased mean corpuscular volume (MCV) is an independent predictor for worse outcomes in coronary artery disease. However, as parameters to classify different types of anemia together with MCV, the relationship between mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and long-term outcomes in acute coronary syndrome (ACS) remains obscure. Moreover, few studies have compared the prognostic value of these red blood cell indices in anemic and nonanemic patients with ACS. Methods and Results: In this single-center observational cohort study, we enrolled 393 patients diagnosed with ACS, including 75 anemic and 318 nonanemic patients. The composite end points were defined as major adverse cardiovascular events (MACEs). After a median follow-up of 31.24 months, Kaplan-Meier survival analysis showed that higher MCV and MCH but not MCHC were significantly associated with increased MACEs in nonanemic ACS patients. Among the enrolled ACS patients without anemia, Cox regression analysis revealed that high MCV and MCH were correlated with increased MACEs after adjustment for cardiovascular risk factors, and receiver operating characteristic (ROC) curve analysis further confirmed the predictive value of high MCV and MCH. In bivariate correlation and linear regression analysis, plasma homocysteine was positively correlated with MCV and MCH but not MCHC in the nonanemic group even after adjusting for age, male sex, BMI, SBP, DBP, smoking, and diabetes. However, MCV, MCH, and MCHC showed no predictive value for MACEs, and no correlation was found between these red blood cell indices and homocysteine in ACS patients with anemia. Conclusion: After adjusting for cardiovascular risk factors, this study showed that higher admission MCV and MCH but not MCHC were independent predictors for long-term MACEs and positively correlated with homocysteine levels in the blood among the nonanemic but not anemic patients with ACS in China.

Sex differences in the impact of day/night distribution of ST-segment elevation myocardial infarction onset on in-hospital outcomes: findings from the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome Project.

BACKGROUND: Circadian system plays an important role in cardiovascular health. Experimental studies have also identified sex differences in circadian system. We aim to explore the impact of sex on the association between symptom-onset pattern of STEMI and in-hospital adverse outcomes in Chinese population. METHODS: Data were used from the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome Project. 18271 STEMI patients undergoing primary percutaneous coronary intervention entered the study, including 14785 (80.9%) men and 3486 (19.1%) women. The outcomes included all-cause mortality and a composite of major adverse cardiovascular and cerebrovascular events (MACCE) during hospitalization. RESULTS: Most participants experienced STEMI onset during 06:00 h to noon, and there was no difference in onset pattern between men and women (p = 0.582). Logistic regression showed that, after adjustment for cardiovascular risk factors, symptom onset time was significantly associated with in-hospital mortality in men, but not in women or the total population. The odds ratios (ORs) for male patients were 1.86 (95% CI 1.05 to 3.27) for midnight to 06:00 h, 1.58 (95% CI 0.95 to 2.64) for 06:00 h to noon, and 0.80 (95% CI 0.49 to 1.73) for 18:00 h to midnight as compared with STEMI presenting during noon to 18:00 h. But symptom onset time was not associated with MACCE in both sexes or the entire cohort. CONCLUSIONS: These findings show that STEMI onset time was independently associated with in-hospital mortality in male Chinese patients, indicating that sex should be taken into account in studying impact of circadian system on myocardial infarction.

Influence of hemoglobin concentration on the in-hospital outcomes in newly diagnosed heart failure patients with atrial fibrillation: Finding from CCC-AF (improving care for cardiovascular disease in China-atrial fibrillation) project.

ABSTRACT: Atrial fibrillation (AF) and heart failure (HF) coexistence is common of clinical significance. Although anemia is a well-recognized risk factor for adverse outcomes, the prognostic value of hemoglobin is controversial in AF and HF. We aimed to determine whether hemoglobin is associated with in-hospital outcomes in such patients.On the basis of the data from the CCC-AF (Improving Care for Cardiovascular Diseases in China-Atrial Fibrillation) project, 2367 inpatients with a definitive diagnosis of AF and HF and record of admission hemoglobin concentration were included. Logistic regression analysis was performed to investigate the relationship between hemoglobin and in-hospital outcomes.All patients were divided into 4 groups according to quartiles of hemoglobin values. Compared with patients with higher hemoglobin, patients with lower hemoglobin had higher proportion of males, heart rate (HR), and diastolic blood pressure (DBP). On the contrary, they had lower age, medical history, left ventricular ejection fraction (LVEF), and brain natriuretic peptide (P < .05). Spearman correlation showed that hemoglobin was negatively correlated with age, LVEF, international normalized ratio, and serum creatinine but positively correlated with HR, DBP, and blood urea nitrogen (P < .05). Multivariable logistic regression analysis revealed that increasing hemoglobin was an independent protective factor for in-hospital outcomes (odds ratio = 0.989; 95% confidence interval: 0.979-1.000; P = .046).Admission hemoglobin concentration was an independent protective factor for in-hospital outcomes in HF patients with AF. Our study indicated that increasing hemoglobin level and improving anemia degree might improve the prognosis of patients with AF and HF.

Serum Anion Gap is Associated with Risk of All-Cause Mortality in Critically Ill Patients with Acute Myocardial Infarction.

PURPOSE: Anion gap (AG) is a valuable and easily obtained clinical tool for differentially diagnosis of acid-base disorders. Current understanding of the prognostic impact of AG on mortality after acute myocardial infarction (AMI) is limited. We aimed to investigate whether AG is a predictor of short-term and long-term all-cause mortality after AMI. PATIENTS AND METHODS: We examined 1806 patients diagnosed with AMI in intensive care unit from the Medical Information Mart for Intensive Care III (MIMIC-III) database. We analyzed the association of AG with 30-day, 180-day and 1-year all-cause mortality on a continuous scale and in categories, using multivariable Cox regression. We utilized restricted cubic splines to evaluate the linearity between hazard ratio (HR) and AG concentrations. RESULTS: AG was associated with a higher risk of 30-day, 180-day and 1-year all-cause mortality, with adjusted HRs of 1.083 (95% CI 1.051 to 1.117), 1.077 (95% CI 1.049 to 1.105), and 1.074 (95% CI 1.047 to 1.101), respectively. The results were consistent in subgroup analyses. The association between AG and all-cause mortality was linear for 180-day and 1-year mortality, and near linear for 30-day mortality, as higher concentrations were associated with high all-cause mortality. When stratified according to quartiles, AG was associated with 30-day mortality (HR[95% CI]: second quartile, 2.243[1.273, 3.955]; third quartile, 3.026[1.763, 5.194]; top quartile, 4.402[2.573, 7.531]), 180-day mortality (HR[95% CI]: second quartile, 1.719[1.118, 2.645]; third quartile, 2.362[1.575, 3.542]; top quartile, 3.116[2.077, 4.676]), and 1-year mortality (HR[95% CI]: second quartile, 1.700[1.143, 2.528]; third quartile, 2.239[1.536, 3.264]; top quartile, 2.876[1.969, 4.201]) using bottom quartile as reference. CONCLUSION: We firstly demonstrated that higher AG was significantly associated with increased 30-day, 180-day and 1-year all-cause mortality in AMI patients. AG as an easily obtained marker is of strong and reliable predictive value for AMI mortality during follow-up.

Simultaneously Enhanced Potential Gradient and Nonlinearity of ZnO Varistor Ceramics by MnO Doping with Nano-Sized ZnO Powders.

ZnO varistor ceramics with a high potential gradient, as well as a high nonlinear coefficient, were reported and analyzed in this paper. With the use of nano-sized ZnO powders, the average grain size was reduced to about 2.6 µm, which successfully raised the potential gradient to 1172 V/mm. Moreover, the nonlinear coefficient increased to 48, and the leakage current was decreased to 8.4 µA/cm2 by doping a moderate amount of MnO (0.9 mol%). This was proven to be caused by the high Schottky barrier height formed at the grain boundary, where the Mn element segregated and, consequently, led to the increased density of interface states. Therefore, this could be considered as a potential method to simultaneously enhance the potential gradient and the nonlinear coefficient of ZnO varistor ceramics.

HDL-C/apoA-I Ratio Is Associated with the Severity of Coronary Artery Stenosis in Diabetic Patients with Acute Coronary Syndrome.

BACKGROUND: Emerging evidence demonstrates that the lipid metabolism in acute coronary syndrome (ACS) patients with type 2 diabetes mellitus (T2DM) differs from nondiabetic patients. However, the distinct lipid profiles and their relationships with the severity of coronary artery stenosis and prognosis in patients with T2DM remain elusive. METHOD AND RESULT: This single-center, prospective cohort study enrolled 468 patients diagnosed with ACS undergoing coronary angiography, consisting of 314 non-DM and 154 DM patients. The HDL-C/apoA-I ratio was significantly higher in DM patients with a multivessel (≥3 affected vessels) lesion than a single-vessel (1-2 affected vessels) lesion. Regression analyses showed that the HDL-C/apoA-I ratio was positively correlated to the number of stenotic coronary arteries in DM patients but not non-DM patients. However, Kaplan-Meier survival analysis revealed no significant difference in the major adverse cardiovascular event rate regarding different HDL-C/apoA-I levels in DM or non-DM ACS patients at the end of the 2-year follow-up. CONCLUSION: A higher HDL-C/apoA-I ratio is associated with increased severity of coronary artery stenosis in DM patients with ACS but not with the rate of major adverse cardiovascular events at the end of the 2-year follow-up.

The relationship between history of thyroid diseases and risk of in-hospital cardiovascular outcomes in patients with atrial fibrillation: Findings From the CCC-AF (Improving Care for Cardiovascular Disease in China-Atrial Fibrillation) Project

Background: Atrial fibrillation (AF) has the close relation to thyroid dysfunction and these two diseases lead to poor cardiovascular outcomes. But the prognostic value of thyroid diseases in AF remains unclear. We aimed to determine whether history of thyroid diseases is associated with risk of in-hospital cardiovascular outcomes in AF.MethodsBased on the data from the CCC-AF (Improving Care for Cardiovascular Diseases in China-Atrial Fibrillation) project, 31,486 inpatients with a definitive diagnosis of AF and record of history of thyroid diseases were included. Logistic regression analysis was performed to investigate the relationship between history of thyroid diseases and risk of in-hospital major adverse cardiovascular events (MACE) in AF.ResultsAmong AF patients, 503 (1.6%) had a history of hypothyroidism, 642 (2.0%) had a history of hyperthyroidism and 30,341 (96.4%) had no thyroid dysfunction. During this hospitalization, 5146 (16.3%) AF patients suffered from MACE. The incidence was 13.1% in hypothyroidism, 16.3% in euthyroidism and 19.0% in hyperthyroidism, in which there was a significant difference among three groups (p=0.028). Multivariable logistic regression analysis revealed that history of hypothyroidism decreased but history of hyperthyroidism increased the risk of in-hospital MACE in AF patients (adjusted odds ratio [OR]=0.603; 95% confidence interval [CI], 0.449–0.811; p=0.001 versus adjusted OR=1.327; 95% CI, 1.060–1.661; p=0.013).ConclusionHistory of hypothyroidism was an independent protective factor, whereas history of hyperthyroidism was an independent risk factor for in-hospital cardiovascular outcomes in AF. Our study indicated that hyperthyroidism should be treated aggressively in order to improve the prognosis of AF. (AU)

Antecedentes: La fibrilación auricular (FA) está estrechamente relacionada con la disfunción tiroidea, y estas 2 enfermedades conducen a resultados cardiovasculares deficientes. Pero el valor pronóstico de las enfermedades tiroideas en la FA sigue sin estar claro. Nuestro objetivo era determinar si la historia de enfermedades tiroideas está asociada con el riesgo de resultados cardiovasculares intrahospitalarios en la FA.MétodosEn base a los datos del proyecto de mejora de la atención de las enfermedades cardiovasculares en China - fibrilación auricular (CCC-FA, por sus siglas en inglés), se incluyeron 31.486 pacientes hospitalizados con un diagnóstico definitivo de FA y un registro de antecedentes de enfermedades tiroideas. Se realizó un análisis de regresión logística para investigar la relación entre la historia de las enfermedades tiroideas y el riesgo de eventos cardiovasculares adversos importantes intrahospitalarios (MACE) en FA.ResultadosEntre los pacientes con FA, 503 (1,6%) tenían antecedentes de hipotiroidismo, 642 (2,0%) antecedentes de hipertiroidismo y 30.341 (96,4%) no tenía disfunción tiroidea. Durante esta hospitalización, 5.146 (16,3%) pacientes con FA sufrieron de MACE. La incidencia fue del 13,1% en hipotiroidismo, del 16,3% en eutiroidismo y del 19,0% en hipertiroidismo, en los que hubo una diferencia significativa entre 3 grupos (p=0,028). El análisis de regresión logística multivariable reveló que la historia de hipotiroidismo disminuyó, pero la historia de hipertiroidismo aumentó el riesgo de MACE intrahospitalario en pacientes con FA (relación de probabilidades ajustadas [OR]: 0,603; intervalo de confianza [IC] del 95%: 0,449-0,811; p=0,001 frente a OR ajustado 1,327; IC del 95%: 1,060-1,661; p=0,013). (AU)

The relationship between history of thyroid diseases and risk of in-hospital cardiovascular outcomes in patients with atrial fibrillation: Findings From the CCC-AF (Improving Care for Cardiovascular Disease in China-Atrial Fibrillation) Project.

BACKGROUND: Atrial fibrillation (AF) has the close relation to thyroid dysfunction and these two diseases lead to poor cardiovascular outcomes. But the prognostic value of thyroid diseases in AF remains unclear. We aimed to determine whether history of thyroid diseases is associated with risk of in-hospital cardiovascular outcomes in AF. METHODS: Based on the data from the CCC-AF (Improving Care for Cardiovascular Diseases in China-Atrial Fibrillation) project, 31,486 inpatients with a definitive diagnosis of AF and record of history of thyroid diseases were included. Logistic regression analysis was performed to investigate the relationship between history of thyroid diseases and risk of in-hospital major adverse cardiovascular events (MACE) in AF. RESULTS: Among AF patients, 503 (1.6%) had a history of hypothyroidism, 642 (2.0%) had a history of hyperthyroidism and 30,341 (96.4%) had no thyroid dysfunction. During this hospitalization, 5146 (16.3%) AF patients suffered from MACE. The incidence was 13.1% in hypothyroidism, 16.3% in euthyroidism and 19.0% in hyperthyroidism, in which there was a significant difference among three groups (p=0.028). Multivariable logistic regression analysis revealed that history of hypothyroidism decreased but history of hyperthyroidism increased the risk of in-hospital MACE in AF patients (adjusted odds ratio [OR]=0.603; 95% confidence interval [CI], 0.449-0.811; p=0.001 versus adjusted OR=1.327; 95% CI, 1.060-1.661; p=0.013). CONCLUSION: History of hypothyroidism was an independent protective factor, whereas history of hyperthyroidism was an independent risk factor for in-hospital cardiovascular outcomes in AF. Our study indicated that hyperthyroidism should be treated aggressively in order to improve the prognosis of AF.

Interferon-γ decreases ATP-binding cassette subfamily G member 1-mediated cholesterol efflux through small ubiquitin-like modifier/ubiquitin-dependent liver X receptor-α degradation in macrophages.

The effects of interferon-γ (IFN-γ) on cholesterol accumulation and the development of foam cells are still unclear. In the present study, we found that IFN-γ promoted liver X receptor (LXR)-α degradation through the ubiquitin-proteasome system in macrophages. The process was dependent on its interactions with phosphorylated signal transducer and activator of transcription 1 (p-STAT1) and protein inhibitor of activated STAT 1 (PIAS1) because both fludarabine and PIAS1 shRNA reversed the decrease in LXR-α protein expression induced by IFN-γ. Additionally, IFN-γ enhanced the interactions of ubiquitin-conjugating enzyme 9 (UBC9), small ubiquitin-like modifier (SUMO)-1 and SUMO-2/3 with LXR-α. Moreover, treatment with shRNA specific for them not only reduced LXR-α polyubiquitination but also reversed the IFN-γ-induced decrease in its expression. Two specific sumoylation sites in LXR-α, K22 and K326, were indispensable for its IFN-γ-induced polyubiquitination because the K22R and K326R mutations inhibited the polyubiquitination and degradation of LXR-α in IFN-γ-treated macrophages. In addition, K22R or K326R mutation almost completely restored ATP-binding cassette subfamily G member 1 (ABCG1)-mediated cholesterol efflux in IFN-γ-treated macrophages. Taken together, these findings indicate that IFN-γ promotes LXR-α degradation through a SUMO-ubiquitin-dependent pathway, which may inhibit cholesterol efflux mediated by ABCG1 from macrophages and promote the development of atherosclerosis.

Baseline plasma fibrinogen is associated with haemoglobin A1c and 2-year major adverse cardiovascular events following percutaneous coronary intervention in patients with acute coronary syndrome: a single-centre, prospective cohort study.

BACKGROUND: Despite revascularisation, a large proportion of acute coronary syndrome (ACS) patients continue to experience major adverse cardiovascular events (MACEs), which are worsened by diabetes mellitus (DM). Fibrinogen (FIB) is a risk factor for MACEs in coronary artery disease and often elevated in DM. However, the relationships between FIB, glucose metabolism (haemoglobin A1c [HbA1c] and fasting blood glucose [FBG]) and MACEs following percutaneous coronary intervention (PCI) in DM, non-DM or whole patients with ACS remains unknown. METHODS: A total of 411 ACS patients undergoing PCI were enrolled in this study. We compared baseline FIB levels between DM (n = 103) and non-DM (n = 308) patients and divided participants into three groups according to FIB level, i.e. FIB-L, FIB-M and FIB-H, to compare baseline characteristics and MACEs. Linear regression analysis of the relationship between glucose metabolism and FIB, Cox regression, survival and landmark analyses of MACEs were also performed over a median of 27.55 months of follow-up. RESULTS: Patients with DM had higher FIB levels than non-DM patients (3.56 ± 0.99 mg/dL vs. 3.34 ± 0.80 mg/dL, P < 0.05). HbA1c and FBG were significantly positively correlated with FIB in whole and DM patients but not in non-DM patients (all P < 0.05). Compared with the FIB-L group, the FIB-M (hazard ratio [HR] 1.797, 95% CI 1.117-2.892, P = 0.016) and FIB-H (HR 1.664, 95% CI 1.002-2.763, P = 0.049) groups were associated with higher MACEs in whole; the FIB-M (HR 7.783, 95% CI 1.012-59.854, P = 0.049) was associated with higher MACEs in DM patients. FIB was not associated with MACEs in non-DM patients. During landmark analysis, FIB showed better predictive value for MACEs after PCI in the first 30 months of follow up than in the subsequent period. CONCLUSION: In this study from China, FIB was positively associated with glucose metabolism (HbA1c and FBG) in whole and DM populations with ACS. Moreover, elevated baseline FIB levels may be an important and independent predictor of MACEs following PCI, especially amongst those with DM. However, as the follow-up period increased, the baseline FIB levels lost their ability to predict MACEs.

Relation of Direct, Indirect, and Total bilirubin to Adverse Long-term Outcomes Among Patients With Acute Coronary Syndrome.

Bilirubin is known as an antioxidant. However, there have been controversies over whether bilirubin is protective against cardiovascular disease or not. In addition, no study has examined the association between subtypes of total bilirubin (direct bilirubin [DB] and indirect bilirubin [IDB]) and long-term outcomes of acute coronary syndrome (ACS) patients. We included 533 consecutive patients with ACS. All the patients were followed up for the composite end point of cardiac death, revascularization, and acute heart failure. At a median follow-up of 2.4 years, Kaplan-Meier curve demonstrated that higher serum DB levels were significantly associated with major adverse cardiac events (MACE) (p <0.05). However, total bilirubin (TB) and IDB were not associated with MACE by Kaplan-Meier analysis. Cox analysis showed that high TB and DB were associated with increased risk of MACE in ACS even after adjustment of cardiovascular risk factors. The receiver operating characteristic curve illustrated that DB had a predictive value of MACE in ACS. In conclusion, we firstly reported that high TB and DB but not IDB were associated with increased risk of MACE in Chinese ACS, and the prognostic value of DB was superior to that of TB or IDB.

Edaravone Exerts Brain Protective Function by Reducing the Expression of AQP4, APP and Aß Proteins.

This study aims to investigate the changes of aquaporin-4 (AQP4), ß-amyloid precursor proteins (APP) and ß-amyloid (Aß) in brain tissues after cerebral ischemiareperfusion injury (CIRI), and evaluate the effect of edaravone. The Middle Cerebral Artery Occlusion was used to establish CIRI in rats. Rats were divided into control, model and edaravone groups. The neurological deficits in the model group were obvious and the neurological score increased compared to the control group, while the neurological deficits of the edaravone group were improved as the neurological score decreased compared to the model group. The number of pyramidel cells in the hippocampus of the model group was significantly decreased whereas edaravone could reverse this decrease. The model group had significantly higher levels of Aß, APP and AQP4 than the control group and edaravone group, suggesting that they might be involved in the neuronal cell damage. Meanwhile, the increased AQP4 might enhance the permeability of cells, and thus cause cell damage and neurological deficit. Conclusively, edaravone could reduce brain edema, protect neuronal cells and improve the neurological impairment of rats possibly by decreasing the expression of Aß, APP and AQP4. Therefore, edaravone may have the potential to treat neurodegenerative diseases (such as Alzheimer's disease).

Thyroid Dysfunction, Neurological Disorder and Immunosuppression as the Consequences of Long-term Combined Stress.

Stress is a powerful modulator of neuroendocrine, behavioral, and immunological functions. So far, the molecular mechanisms of response to stressors still remain elusive. In the current study, after 10 days of repeated chronic stress (hot-dry environment and electric foot-shock), a murine model of combined-stress (CS) was created in the SPF Wistar rats. Meanwhile, we established an ulcerative-colitis (UC) rat model induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS)/ethanol enema according to previous studies. The blood, hypothalamus, and colon tissues of these rats from CS, normal control (NC), UC and sham (SH) groups, were collected for further investigations. Comparing to the NC group, the serum levels of T3, T4, fT3 and fT4 were obviously decreased in the CS group after chronic stress, indicating that thyroid dysfunction was induced by long-term combined stress. Moreover, the application of RNA-seq and subsequent analyses revealed that neurological disorder and immunosuppression were also caused in the hypothalamus and colon tissues, respectively. Comparing with SH group, besides the induced colon inflammation, thyroid dysfuntion and neurological disorder were also produced in the UC group, suggesting that hypothalamic-pituitary-thyroid (HPT) axis and gastrointestinal system might not function in isolation, but rather, have intricate crosstalks.

[Genetic polymorphism of 19 STR loci in Xinjiang Barkol Kazakh population].

OBJECTIVE: To investigate 19 short tandem repeat (STR) loci in Chinese Kazakh population in Barkol County with Goldeneye™20A multiplex amplification system. METHODS: DNA samples were screened from 81 unrelated individuals. The 19 loci were D8S1179, D21S11, CSF1PO, D3S1358, D7S820, TH01, D13S317, D2S1338, D18S51, D16S539, TPOX, vWA, D19S433, D5S818, PentaD, PentaE, D6S1043, D12S391 and FGA. The PCR products were analyzed and genotyped by ABI3130XL sequencer. RESULTS: These loci were highly polymorphic. The combined power of discrimination was 0.999999999 and the combined paternity of exclusion was 0.999998914. CONCLUSION: Goldeneye™20A multiplex amplification system is very useful in forensic case investigation for Barkol Kazakh population.