共查询到20条相似文献,搜索用时 0 毫秒
1.
Dominik Bergis Valentin Kassis Annika Ranglack Verena Koeberle Albrecht Piiper Bernd Kronenberger Stefan Zeuzem Oliver Waidmann Heinfried H Radeke 《Translational oncology》2013,6(3):311-318
BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor, usually arises in the setting of liver cirrhosis (LC), and has a poor prognosis. The recently discovered Th2-cytokine interleukin-33 (IL-33) is a possible mediator in pancreatic and gastric carcinogeneses. IL-33 binds to its receptor and to soluble ST2 (sST2), which thereby acts as a regulator. The role of IL-33 and sST2 in HCC has not been elucidated yet. METHODS: We conducted a case-control study with 130 patients and 50 healthy controls (HCs). Sixty-five patients suffered from HCC and 65 patients had LC without HCC. We assessed serum IL-33 and sST2 levels and their association with established prognostic scores, liver function parameters, and overall survival (OS). RESULTS: No significant difference in IL-33 serum levels was found in HCC compared to LC and HCs. IL-33 levels did not correlate with OS, liver function parameters, the Model for End-Stage Liver Disease (MELD) score, or the Cancer of the Liver Italian Program (CLIP) score. sST2 levels were significantly elevated in LC and HCC patients compared to HCs (P < .0001). Mean sST2 levels in LC were higher than in HCC (P < .0001), but a significant association with OS was only observed in the HCC group (P = .003). sST2 in HCC correlated with the CLIP score, the MELD score, and liver function parameters. CONCLUSION: In the present study, the serum concentration of sST2 was associated with OS of HCC. Therefore, sST2 may be considered as a new prognostic marker in HCC and is worth further evaluation. 相似文献
2.
José Tu?ón Carmen Cristóbal Nieves Tarín álvaro Ace?a María Luisa González-Casaus Ana Huelmos Joaquín Alonso óscar Lorenzo Emilio González-Parra Ignacio Mahíllo-Fernández Ana María Pello Rocío Carda Jerónimo Farré Fernando Rodríguez-Artalejo Lorenzo López-Bescós Jesús Egido 《PloS one》2014,9(4)
Objective
Vitamin D and fibroblast growth factor-23 (FGF-23) are related with cardiovascular disorders. We have investigated the relationship of calcidiol (vitamin D metabolite) and FGF-23 plasma levels with the incidence of adverse outcomes in patients with coronary artery disease.Methods
Prospective follow-up study of 704 outpatients, attending the departments of Cardiology of four hospitals in Spain, 6–12 months after an acute coronary event. Baseline calcidiol, FGF-23, parathormone, and phosphate plasma levels were assessed. The outcome was the development of acute ischemic events (any acute coronary syndrome, stroke, or transient ischemic attack), heart failure, or death. Cox regression adjusted for the main confounders was performed.Results
Calcidiol levels showed a moderate-severe decrease in 57.3% of cases. Parathormone, FGF-23, and phosphate levels were increased in 30.0%, 11.5% and 0.9% of patients, respectively. Only 22.4% of patients had glomerular filtration rate<60 ml/min1.73 m2. After a mean follow-up was 2.15±0.99 years, 77 patients developed the outcome. Calcidiol (hazard ratio [HR] = 0.67; 95% confidence interval [CI] = 0.48–0.94; p = 0.021) and FGF-23 (HR = 1.13; 95% CI = 1.04–1.23; p = 0.005) plasma levels predicted independently the outcome. There was a significant interaction between calcidiol and FGF-23 levels (p = 0.025). When the population was divided according to FGF-23 levels, calcidiol still predicted the outcome independently in patients with FGF-23 levels higher than the median (HR = 0.50; 95% CI = 0.31–0.80; p = 0.003) but not in those with FGF-23 levels below this value (HR = 1.03; 95% CI = 0.62–1.71; p = 0.904).Conclusions
Abnormalities in mineral metabolism are frequent in patients with stable coronary artery disease. In this population, low calcidiol plasma levels predict an adverse prognosis in the presence of high FGF-23 levels. 相似文献3.
Ivo A. Joosen Frank Schiphof Mathijs O. Versteylen Eduard M. Laufer Mark H. Winkens Patricia J. Nelemans Jeroen P. Kooman Leonard Hofstra Joachim E. Wildberger Tim Leiner 《PloS one》2012,7(10)
Background
Both end-stage and milder stages of chronic kidney disease (CKD) are associated with an increased risk of adverse cardiovascular events. Several studies found an association between decreasing renal function and increasing coronary artery calcification, but it remains unclear if this association is independent from traditional cardiovascular risk factors. Therefore, the aim of this study was to investigate whether mild to moderate CKD is independently associated with coronary plaque burden beyond traditional cardiovascular risk factors.Methods
A total of 2,038 patients with symptoms of chest discomfort suspected for coronary artery disease underwent coronary CT-angiography. We assessed traditional risk factors, coronary calcium score and coronary plaque characteristics (morphology and degree of luminal stenosis). Patients were subdivided in three groups, based on their estimated glomerular filtration rate (eGFR) Normal renal function (eGFR ≥90 mL/min/1.73 m2); mild CKD (eGFR 60–89 mL/min/1.73 m2); and moderate CKD (eGFR 30–59 mL/min/1.73 m2).Results
Coronary calcium score increased significantly with decreasing renal function (P<0.001). Coronary plaque prevalence was higher in patients with mild CKD (OR 1.83, 95%CI 1.52–2.21) and moderate CKD (OR 2.46, 95%CI 1.69–3.59), compared to patients with normal renal function (both P<0.001). Coronary plaques with >70% luminal stenosis were found significantly more often in patients with mild CKD (OR 1.67 (95%CI 1.16–2.40) and moderate CKD (OR2.36, 95%CI 1.35–4.13), compared to patients with normal renal function (both P<0.01). After adjustment for traditional cardiovascular risk factors, the association between renal function and the presence of any coronary plaque as well as the association between renal function and the presence of coronary plaques with >70% luminal stenosis becomes weaker and were no longer statistically significant.Conclusion
Although decreasing renal function is associated with increasing extent and severity of coronary artery disease, mild to moderately CKD is not independently associated with coronary plaque burden after adjustment for traditional cardiovascular risk factors. 相似文献4.
Hayakawa H Hayakawa M Kume A Tominaga S 《The Journal of biological chemistry》2007,282(36):26369-26380
The ST2 gene produces a soluble secreted form and a transmembrane form, referred to as soluble ST2 and ST2L, respectively. A recent study has reported that interleukin (IL)-33 is a specific ligand of ST2L and induces production of T helper type 2 (Th2) cytokines. Although soluble ST2 is highly produced in sera of asthmatic patients and plays a critical role for production of Th2 cytokines, the function of soluble ST2 in relation to IL-33 signaling remains unclear. Here we show antagonistic effects of soluble ST2 on IL-33 signaling using a murine thymoma EL-4 cells stably expressing ST2L and a murine model of asthma. Soluble ST2 directly bound to IL-33 and suppressed activation of NF-kappaB in EL-4 cells stably expressing ST2L, suggesting that the complex of soluble ST2 and IL-33 fails to bind to ST2L. In a murine model of asthma, pretreatment with soluble ST2 reduced production of IL-4, IL-5, and IL-13 from IL-33-stimulated splenocytes. These results indicate that soluble ST2 acts as a negative regulator of Th2 cytokine production by the IL-33 signaling. Our study provides a molecular mechanism wherein soluble ST2 modulates the biological activity of IL-33 in allergic airway inflammation. 相似文献
5.
Giuseppe Maiolino Luigi Pedon Maurizio Cesari Anna Chiara Frigo Robert L. Wolfert Marlena Barisa Leopoldo Pagliani Giacomo Rossitto Teresa Maria Seccia Mario Zanchetta Gian Paolo Rossi 《PloS one》2012,7(10)
Objective
Lipoprotein-associated phospholipase A2 (Lp-PLA2) is deemed to play a role in atherosclerosis and plaque destabilization as demonstrated in animal models and in prospective clinical studies. However, most of the literature is either focused on high-risk, apparently healthy patients, or is based on cross sectional studies. Therefore, we tested the hypothesis that serum Lp-PLA2 mass and activity are useful for predicting cardiovascular (CV) events over the coronary atherosclerotic burden and conventional risk factors in high-risk coronary artery disease patients.Methods and Results
In a prospective cohort study of 712 Caucasian patients, who underwent coronary angiography and measurement of both Lp-PLA2 mass and activity at baseline, we determined incident CV events at follow-up after splitting the patients into a high and a low Lp-PLA2 mass and activity groups based on ROC analysis and Youden index. Kaplan-Meier and propensity score matching analysis were used to compare CV event-free survival between groups. Follow-up data were obtained in 75% of the cohort after a median of 7.2 years (range 1–12.7 years) during which 129 (25.5%) CV events were observed. The high Lp-PLA2 activity patients showed worse CV event-free survival (66.7% vs. 79.5%, p = 0.023) and acute coronary syndrome-free survival (75.4% vs. 85.6%, p = 0.04) than those in low Lp-PLA2 group.Conclusions
A high Lp-PLA2 activity implies a worse CV prognosis at long term follow up in high-risk Caucasian patients referred for coronary angiography. 相似文献6.
Katie Stone Emily Woods Susann M. Szmania Owen W. Stephens Tarun K. Garg Bart Barlogie John D. Shaughnessy Jr Brett Hall Manjula Reddy Antje Hoering Emily Hansen Frits van Rhee 《PloS one》2013,8(1)
Multicentric Castleman Disease is largely driven by increased signaling in the pathway for the plasma cell growth factor interleukin-6. We hypothesized that interleukin-6/interleukin-6 receptor/gp130 polymorphisms contribute to increased interleukin-6 and/or other components of the interleukin-6 signaling pathway in HIV-negative Castleman Disease patients. The study group was composed of 58 patients and 50 healthy donors of a similar racial/ethnic profile. Of seven polymorphisms chosen for analysis, we observed an increased frequency between patients and controls of the minor allele of interleukin-6 receptor polymorphism rs4537545, which is in linkage disequilibrium with interleukin-6 receptor polymorphism rs2228145. Further, individuals possessing at least one copy of the minor allele of either polymorphism expressed higher levels of soluble interleukin-6 receptor. These elevated interleukin-6 receptor levels may contribute to increased interleukin-6 activity through the trans-signaling pathway. These data suggest that interleukin-6 receptor polymorphism may be a contributing factor in Castleman Disease, and further research is warranted. 相似文献
7.
8.
9.
Xin Tu Shaofang Nie Yuhua Liao Hongsong Zhang Qian Fan Chengqi Xu Ying Bai Fan Wang Xiang Ren Tingting Tang Ni Xia Sisi Li Yuan Huang Juan Liu Qing Yang Yuanyuan Zhao Qiulun Lv Qingxian Li Yue Li Yunlong Xia Jin Qian Bin Li Gang Wu Yanxia Wu Yan Yang Qing K. Wang Xiang Cheng 《American journal of human genetics》2013
10.
Xin Tu Shaofang Nie Yuhua Liao Hongsong Zhang Qian Fan Chengqi Xu Ying Bai Fan Wang Xiang Ren Tingting Tang Ni Xia Sisi Li Yuan Huang Juan Liu Qing Yang Yuanyuan Zhao Qiulun Lv Qingxian Li Yue Li Yunlong Xia Jin Qian Bin Li Gang Wu Yanxia Wu Yan Yang Qing?K. Wang Xiang Cheng 《American journal of human genetics》2013,93(4):652-660
The effects of interleukin-33 (IL-33) on the immune system have been clearly demonstrated; however, in cardiovascular diseases, especially in coronary artery disease (CAD), these effects have not yet been clarified. In this study, we investigate the genetic role of the IL-33-ST2L pathway in CAD. We performed three-stage case-control association analyses on a total of 4,521 individuals with CAD and 4,809 controls via tag SNPs in the genes encoding IL-33 and ST2L-IL-1RL1. One tag SNP in each gene was significantly associated with CAD (rs7025417T in IL33, padj = 1.19 × 10−28, OR = 1.39, 95% CI: 1.31–1.47; rs11685424G in IL1RL1, padj = 6.93 × 10−30, OR = 1.40, 95% CI: 1.32–1.48). Combining significant variants in two genes, the risk for CAD increased nearly 5-fold (padj = 8.90 × 10−21, OR = 4.98, 95% CI: 3.56–6.97). Traditional risk factors for CAD were adjusted for the association studies by SPSS with logistic regression analysis. With the two variants above, both located within the gene promoter regions, reporter gene analysis indicated that the rs7025417 C>T and rs11685424 A>G changes resulted in altered regulation of IL33 and IL1RL1 gene expression, respectively (p < 0.005). Further studies revealed that the rs7025417 genotype was significantly associated with plasma IL-33 levels in the detectable subjects (n = 227, R2 = 0.276, p = 1.77 × 10−17): the level of IL-33 protein increased with the number of rs7025417 risk (T) alleles. Based on genetic evidence in humans, the IL-33-ST2L pathway appears to have a causal role in the development of CAD, highlighting this pathway as a valuable target for the prevention and treatment of CAD. 相似文献
11.
Xin Tu Shaofang NieYuhua Liao Hongsong ZhangQian Fan Chengqi XuYing Bai Fan WangXiang Ren Tingting TangNi Xia Sisi LiYuan Huang Juan LiuQing Yang Yuanyuan ZhaoQiulun Lv Qingxian LiYue Li Yunlong XiaJin Qian Bin LiGang Wu Yanxia WuYan Yang Qing K. Wang Xiang Cheng 《American journal of human genetics》2014
12.
Jiri F. P. Wagenaar M. Hussein Gasem Marga G. A. Goris Mariska Leeflang Rudy A. Hartskeerl Tom van der Poll Cornelis van 't Veer Eric C. M. van Gorp 《PLoS neglected tropical diseases》2009,3(6)
Background
Severe leptospirosis features bleeding and multi-organ failure, leading to shock and death. Currently it is assumed that both exaggerated inflammation and immune suppression contribute to mortality in sepsis. Indeed, several proinflammatory cytokines are reported to be induced during leptospirosis. Toll-like receptors, which play an important role in the initiation of an innate immune response, are inhibited by negative regulators including the membrane-bound ST2 (mST2) receptor. Soluble ST2 (sST2) has been implicated to inhibit signaling through mST2. The aim of this study was to determine the extent of sST2 and (pro-) inflammatory cytokine release in patients with severe leptospirosis.Methodology and Principal Findings
In an observational study, 68 consecutive cases of severe leptospirosis were included. Soluble ST2 and cytokines (TNF-α, IL-1β, IL-6, IL-8, and IL-10) were repeatedly measured. To determine whether blood cells are a source of sST2 during infection, we undertook an in vitro experiment: human whole blood and peripheral blood mononuclear cells (PBMC) were stimulated with viable pathogenic Leptospira. All patients showed elevated sST2, IL-6, IL-8, and IL-10 levels on admission. Admission sST2 levels correlated with IL-6, IL-8, and IL-10. Thirty-four patients (50%) showed clinical bleeding. Soluble ST2 levels were significantly associated with bleeding overall (OR 2.0; 95%CI: 1.2–3.6) and severe bleeding (OR 5.1; 95%CI: 1.1–23.8). This association was unique, since none of the cytokines showed this correlation. Moreover, sST2 was associated with mortality (OR 2.4; 95%CI: 1.0–5.8). When either whole blood or isolated PBMCs were stimulated with Leptospira in vitro, no sST2 production could be detected.Conclusions
Patients with severe leptospirosis demonstrated elevated plasma sST2 levels. Soluble ST2 levels were associated with bleeding and mortality. In vitro experiments showed that (white) blood cells are probably not the source. In this regard, sST2 could be an indicative marker for tissue damage in patients suffering from severe leptospirosis. 相似文献13.
Soo Youn Lee Seung-Jin Oh Eung Ju Kim Chi-Yoon Oum Sung Hwan Park Jaewon Oh Jung-Sun Kim Byeong-Keuk Kim Sungha Park Hyuk-Jae Chang Geu-Ru Hong Young-Guk Ko Seok-Min Kang Donghoon Choi Jong-Won Ha Myeong-Ki Hong Yangsoo Jang Namsik Chung Sang-Hak Lee 《PloS one》2016,11(11)
BackgroundAlthough intensive statin therapy is recommended for high risk patients, evidence of its benefit in patients with stable coronary artery disease (CAD) and very low low-density lipoprotein-cholesterol (LDL-C) has been very rare. In this study, we investigated whether higher statin intensity reduces cardiovascular risks in this population.MethodsIn this retrospective study, a total of 5234 patients with stable CAD were screened at three tertiary hospitals in Korea; 449 patients (mean age: 65 years, male: 69%) with LDL-C <80 mg/dL were finally analyzed. The statin intensities were classified according to the 2013 American College of Cardiology/American Heart Association guidelines. Patients who received statins equivalent to or weaker than atorvastatin 10 mg (group 1) were compared with those who took statins equivalent to or stronger than atorvastatin 20 mg (group 2). The impact of statin intensity on major adverse cardiac events (MACE) was evaluated during follow-up.ResultsGroup 1 and group 2 consisted of 181 patients (40.3%) and 268 patients (59.7%), respectively. The mean LDL-C level decreased to 52 and 57 mg/dL in group 1 and group 2, respectively, during follow-up. In a median follow-up of 4.5 years, patients of group 2 had a lower incidence of MACE (30 [16.6%] vs. 12 [4.5%], p <0.001), which were mostly related to a lower incidence of coronary revascularization. Cox proportional hazard analyses identified the statin intensity of group 2 (adjusted hazard ratio: 0.25, confidence interval: 0.11–0.55, p <0.001) and the baseline high-density lipoprotein-cholesterol level as independent determinants of MACE.ConclusionThis study provides evidence that higher intensity statins are beneficial for cardiovascular outcomes in patients with stable CAD and very low LDL-C. Statins equivalent to or stronger than atorvastatin 20 mg are more effective than lower intensity statins. 相似文献
14.
15.
Fumihiko Takeuchi Masato Isono Tomohiro Katsuya Mitsuhiro Yokota Ken Yamamoto Toru Nabika Kazuro Shimokawa Eitaro Nakashima Takao Sugiyama Hiromi Rakugi Shuhei Yamaguchi Toshio Ogihara Yukio Yamori Norihiro Kato 《PloS one》2012,7(9)
Background/Objective
In Japanese populations, we performed a replication study of genetic loci previously identified in European-descent populations as being associated with lipid levels and risk of coronary artery disease (CAD).Methods
We genotyped 48 single nucleotide polymorphisms (SNPs) from 22 candidate loci that had previously been identified by genome-wide association (GWA) meta-analyses for low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and/or triglycerides in Europeans. We selected 22 loci with 2 parallel tracks from 95 reported loci: 16 significant loci (p<1×10−30 in Europeans) and 6 other loci including those with suggestive evidence of lipid associations in 1292 GWA-scanned Japanese samples. Genotyping was done in 4990 general population samples, and 1347 CAD cases and 1337 controls. For 9 SNPs, we further examined CAD associations in an additional panel of 3052 CAD cases and 6335 controls.Principal Findings
Significant lipid associations (one-tailed p<0.05) were replicated for 18 of 22 loci in Japanese samples, with significant inter-ethnic heterogeneity at 4 loci–APOB, APOE-C1, CETP, and APOA5–and allelic heterogeneity. The strongest association was detected at APOE rs7412 for LDL-C (p = 1.3×10−41), CETP rs3764261 for HDL-C (p = 5.2×10−24), and APOA5 rs662799 for triglycerides (p = 5.8×10−54). CAD association was replicated and/or verified for 4 loci: SORT1 rs611917 (p = 1.7×10−8), APOA5 rs662799 (p = 0.0014), LDLR rs1433099 (p = 2.1×10−7), and APOE rs7412 (p = 6.1×10−13).Conclusions
Our results confirm that most of the tested lipid loci are associated with lipid traits in the Japanese, further indicating that in genetic susceptibility to lipid levels and CAD, the related metabolic pathways are largely common across the populations, while causal variants at individual loci can be population-specific. 相似文献16.
Elevated Plasma Soluble ST2 Is Associated with Heart Failure Symptoms and Outcome in Aortic Stenosis
Patrizio Lancellotti Raluca Dulgheru Julien Magne Christine Henri Laurence Servais Nassim Bouznad Arnaud Ancion Christophe Martinez Laurent Davin Caroline Le Goff Alain Nchimi Luc Piérard Cécile Oury 《PloS one》2015,10(9)
B-type natriuretic peptide (BNP) is often used as a complementary finding in the diagnostic work-up of patients with aortic stenosis (AS). Whether soluble ST2, a new biomarker of cardiac stretch, is associated with symptomatic status and outcome in asymptomatic AS is unknown. sST2 and BNP levels were measured in 86 patients (74±13 years; 59 asymptomatic, 69%) with AS (<1.5 cm2) and preserved left ventricular ejection fraction who were followed-up for 26±16 months. Both BNP and sST2 were associated with NYHA class but sST2 (>23 ng/mL, AUC = 0.68, p<0.01) was more accurate to identify asymptomatic patients or those who developed symptoms during follow-up. sST2 was independently related to left atrial index (p<0.0001) and aortic valve area (p = 0.004; model R2 = 0.32). A modest correlation was found with BNP (r = 0.4, p<0.01). During follow-up, 29 asymptomatic patients (34%) developed heart failure symptoms. With multivariable analysis, peak aortic jet velocity (HR = 2.7, p = 0.007) and sST2 level (HR = 1.04, p = 0.03) were independent predictors of cardiovascular events. In AS, sST2 levels could provide complementary information regarding symptomatic status, new onset heart failure symptoms and outcome. It might become a promising biomarker in these patients. 相似文献
17.
18.
19.
Konstantin A. Krychtiuk Stefan P. Kastl Stefan Pfaffenberger Max Lenz Sebastian L. Hofbauer Anna Wonnerth Lorenz Koller Katharina M. Katsaros Thomas Pongratz Georg Goliasch Alexander Niessner Ludovit Gaspar Kurt Huber Gerald Maurer Elisabeth Dostal Johann Wojta Stanislav Oravec Walter S. Speidl 《PloS one》2015,10(4)
Objective
Atherosclerosis is considered to be an inflammatory disease in which monocytes and monocyte-derived macrophages play a key role. Circulating monocytes can be divided into three distinct subtypes, namely in classical monocytes (CM; CD14++CD16-), intermediate monocytes (IM; CD14++CD16+) and non-classical monocytes (NCM; CD14+CD16++). Low density lipoprotein particles are heterogeneous in size and density, with small, dense LDL (sdLDL) crucially implicated in atherogenesis. The aim of this study was to examine whether monocyte subsets are associated with sdLDL serum levels.Methods
We included 90 patients with angiographically documented stable coronary artery disease and determined monocyte subtypes by flow cytometry. sdLDL was measured by an electrophoresis method on polyacrylamide gel.Results
Patients with sdLDL levels in the highest tertile (sdLDL≥4mg/dL;T3) showed the highest levels of pro-inflammatory NCM (15.2±7% vs. 11.4±6% and 10.9±4%, respectively; p<0.01) when compared with patients in the middle (sdLDL=2-3mg/dL;T2) and lowest tertile (sdLDL=0-1mg/dL;T1). Furthermore, patients in the highest sdLDL tertile showed lower CM levels than patients in the middle and lowest tertile (79.2±8% vs. 83.9±7% and 82.7±5%; p<0.01 for T3 vs. T2+T1). Levels of IM were not related to sdLDL levels (5.6±4% vs. 4.6±3% vs. 6.4±3% for T3, T2 and T1, respectively). In contrast to monocyte subset distribution, levels of circulating pro- and anti-inflammatory markers were not associated with sdLDL levels.Conclusion
The atherogenic lipoprotein fraction sdLDL is associated with an increase of NCM and a decrease of CM. This could be a new link between lipid metabolism dysregulation, innate immunity and atherosclerosis. 相似文献20.
Klaus Stark Wibke Reinhard Martina Grassl Jeanette Erdmann Heribert Schunkert Thomas Illig Christian Hengstenberg 《PloS one》2009,4(11)